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In children, hypothyroidism usually presents non-specific symptoms; symptoms can emerge gradually, compromising a timely diagnosis. We report the case of a 13-year-old male, who was admitted to the hospital due to swelling of the torso and neck. Besides these symptoms, the child was healthy, except for a significant growth delay. Ultrasound evaluation and blood tests led to the diagnosis of myxedema secondary to severe hypothyroidism, which was due to autoimmune thyroiditis. Further investigations revealed pericardial effusion and pituitary hyperplasia, with hyper-prolactinemia. Treatment with levothyroxine led to edema regression and clinical, hemato-chemical and radiological improvement. After 6 months, growth velocity increased, although the recovery of growth already lost was not guaranteed. Brain MRI showed regression of pituitary hyperplasia. The diagnostic delay in this case was probably due to the patient’s apparent good health, and the underestimation of growth restriction. This report underlines the importance of growth monitoring in adolescence, a critical period for identifying endocrine conditions; if undiagnosed, these conditions can lead to serious complications, such as myxedema in hypothyroidism, with potential effects beyond growth on multiple organs.

Pituitary hyperplasia following primary hypothyroidism in pediatric age group population is considered rare with reports of unnecessary neurosurgical intervention for this medically treatable condition. Given the paucity of information on this topic, it is timely to provide clinicians with a comprehensive summary of available research. A search of published studies in Pubmed, PsychInfo and Cochrane Database with the terms “pituitary hyperplasia” or “pituitary hypertrophy” and “hypothyroidism” was performed and the results filtered for English language, pediatric (0-18 years) population and CT or MRI confirmed findings. 55 studies met the inclusion criteria. Data for a total of 110 patients with pituitary hyperplasia following primary hypothyroidism were extracted. The study population included 29 males and 81 females (M: F= 0.35:1). Patient age varied from 3 weeks to 18 years with a mean age of 10.22 years. The most common clinical presentations included growth retardation, constipation and features of myxedema which were present in 78, 36 and 18 percent of children included in our review. Neuroimaging showed the mean (SD) pituitary height being 13.48 mm (4.72 mm). All of the patients achieved resolution of their pituitary mass and clinical as well as biochemical abnormalities 1 to 26 months after initiation of thyroid hormone replacement therapy, with an average time interval of 7.22 months. Our review has tried to delve in the pathophysiology as well as clinical, biochemical and radiological aspects of pediatric pituitary hyperplasia secondary to primary hypothyroidism and provide recommendations for treatment and follow-up. This may help anyone concerned gain a substantial knowledge on this topic.

The syndrome of inappropriate thyroid-stimulating hormone (TSH) secretion is characterized by high circulating thyroid hormone concentrations in the presence of non-suppressed TSH. After exclusion of the laboratory interference, TSH-secreting pituitary adenoma (TSHoma) or resistance to thyroid hormone-beta (RTH-β) should be suspected. The presence of a pituitary adenoma on the hypothalamic-pituitary imaging supports the diagnosis of TSHoma. However, the incidental findings of non-functioning pituitary adenomas may appear in patients with RTH-β. Abnormal MRI finding in the RTH-β patient also includes pituitary enlargement from thyrotroph hyperplasia. We herein reported a patient with inappropriate TSH secretion who has pituitary hyperplasia mimicking TSHoma. This case illustrates the diagnostic tests to distinguish an RTH-β from TSHoma.

Background Pituitary hyperplasia (PH) is a non-neoplastic increase in one or more cell subtype of the adenohypophysis. It is physiologically seen in pregnancy from resultant lactotroph hyperplasia and pathologically in organ dysfunctions that lead to loss of negative feedback on hypothalamus like primary hypothyroidism and primary adrenal insufficiency. Although primary hypothyroidism is common, PH is an under-recognized consequence of long-standing hypothyroidism. Case Description A 26-year-old female with class 3 obesity, type 2 diabetes mellitus, and primary hypothyroidism on replacement presented for evaluation of secondary amenorrhea. Two months prior to presentation, she underwent a brain MRI for new-onset headache which revealed diffusely enhancing homogenous pituitary tissue measuring 2.3 cm with upward lifting of the optic chiasm. Serum prolactin was elevated at 86.2 ng/ml (2.8-26 ng/ml). This was presumed to be secondary to a prolactinoma and cabergoline was started by the referring provider. Subsequent workup revealed elevated thyroid-stimulating hormone (TSH) at 494.11 mU/L (0.30- 4.00 mU/L) and a low free thyroxine (FT4) of 0.2 ng/dl (0.8-1.7 ng/dl). Other pituitary hormones were within normal limits. The visual field examination was normal. It was noted she had a persistently elevated TSH over the past five years. On further questioning, the patient ran out of levothyroxine replacement 6 months ago and had been generally non-adherent to therapy for years due to nausea. Improved medication adherence resulted in the normalization of prolactin and reduction in TSH level. Repeat MRI 2 months later revealed a reduction in her pituitary hyperplasia to 2.1 cm. Discussion In severe primary hypothyroidism, there is loss of negative feedback to the hypothalamus due to low circulating FT4 and triiodothyronine (T3) concentrations. As a result, there is stimulation of thyrotropin-releasing hormone (TRH) which promotes thyrotroph hyperplasia. A strong correlation exists between TSH concentration and the degree of pituitary hyperplasia. The typical MRI finding is a diffusely enhancing homogenous pituitary mass. Despite optic chiasm contact, physiologic pituitary hyperplasia rarely causes visual field defects. High concentrations of TRH stimulates prolactin release with resultant mild hyperprolactinemia. Although PH is reversible with therapy, rare cases with subsequent development of panhypopituitarism while on therapy have been reported in the setting of longstanding hypothyroidism. Very rarely, chronically untreated primary hypothyroidism can stimulate the growth of a thyrotroph adenoma. Long-term biochemical and radiological monitoring is therefore recommended until resolution. This case highlights the physiologic responses manifested in severe primary hypothyroidism and the fact that these changes improve with adequate replacement.

17 year old female presented for evaluation of galactorrhea of 3 months duration. Patient was diagnosed with papillary thyroid cancer and underwent total thyroidectomy in 2011. She was prescribed Synthroid 175 mcg but was not compliant with taking her medicine. In April 2019 she developed bilateral galactorrhea for which she was evaluated at an outside facility and was found to have a prolactin 143.7ng/mL (n 7.2-63) and TSH 996 mIU/L (n 0.5 -4.0). Pituitary MRI revealed pituitary macroadenoma measuring 1.5 x 1.4 x 1.2 cm with slight elevation of the optic chiasm and infundibulum. She was advised to restart Synthroid and was referred for the neurosurgery team at our facility for surgical resection of pituitary macroadenoma. Over the same period of time, she gained 25 lbs, developed headaches, excessive fatigue, constipation, hair loss, lower extremity swelling, and puffiness of her face. Her menstrual cycles were regular but this was only after she was placed on norelgestromin/ ethinyl estradiol transdermal patch. She denied visual changes. By the time she was seen at our clinic in June 2019, she was taking Synthroid daily for 1 month. TSH decreased to 1.0 mIU/L and prolactin improved to 68 ng/mL. IGF-1 was low at 98 ng/mL (n 149-509). ACTH, morning cortisol, and 24 hour urine free cortisol were within reference range. Visual field testing showed no visual defects. We advised patient to continue taking Synthroid and to follow up in 1 month. On the follow up visit in July 2019, TSH was 0.2 mIU/L, prolactin was 52 ng/mL and IGF-1 was 105 ng/mL. Pituitary MRI showed pituitary hyperplasia that has decreased compared to previous MRI, now measuring around 1 cm at the largest dimension without contact with the optic chiasm and the Infundibulum was at midline. Galactorrhea and headaches resolved and fatigue significantly improved.

Pituitary hyperplasia as a result of autoimmune thyroiditis has been rarely reported in children. We report a prepubertal girl with Hashimoto’s thyroiditis who was inadvertently diagnosed to have a pituitary macroadenoma based on neuroimaging.

Background: Pathologic pituitary hyperplasia (PH) in Pediatrics may be observed in several clinical settings. In PH secondary to primary hypothyroidism the increased TRH levels, due to a long-standing hypothyroidism state and loss of negative thyroxin feedback, causes thyrotroph and lactotroph cells hypertrophy, leading to an enlarged pituitary gland. Herein we report on two pediatric patients presenting this condition. Patient 1: A 9 year-old female was referred due to severe short stature (height Z-score: -5 SDS), face myxedema and a suprasellar mass on MRI. She had a past of headache, fatigue and learning disabilities. Laboratory evaluation showed anaemia and dyslipidemia (total cholesterol 282 mg/ dL, LDL 222 mg/dL); severe hypothyroidism: TSH 1,300 IU/L (NR 0.27-4.2), fT4 0.14 ng/dL (NR 0.93-1.7), negative thyroid antibodies TgAb 0.9 mcg/L (NR

Pituitary hyperplasia is defined as an absolute increase in the number of one or more adenohypophyseal cell subtypes, manifesting radiologically as pituitary enlargement beyond what is considered normal. It has been noted in certain physiological conditions like pregnancy however can also be seen in pathological conditions with end organ insufficiency like severe hypothyroidism. 21- year old female with a past medical history of Primary Hypothyroidism secondary to Hashimoto’s thyroiditis presented initially for evaluation of worsening headache and blurry vision. She was diagnosed with hypothyroidism at 10 years of age and had an extensive family history of hypothyroidism. At the time of presentation, she was 11 months post- partum and had been on and off her levothyroxine supplementation, having stopped it completely for a few months after delivery. MRI brain showed an 18 mm homogeneously enhancing intrasellar mass with suprasellar extension. She was referred to Neurosurgery for further evaluation. Workup revealed a TSH >100 (0.27 - 4.2 mIU/L) and FT4 Prolonged primary hypothyroidism leads to pituitary hyperplasia due to loss of negative feedback from lack of circulating T4 and T3, leading to excessive TRH secretion from the hypothalamus. The high TRH can lead to thyrotroph as well as lactotroph hyperplasia. Subsequently patients can present with headache, vision changes along with signs and symptoms of hypothyroidism and increased prolactin secretion. It is important to differentiate hyperplasia from other sellar lesions like pituitary macroadenoma or hypophysitis. Patients with hypothyroidism, who have pituitary enlargement diagnosed on brain imaging, should be promptly diagnosed and treated with thyroid hormone replacement. With a higher frequency and improved quality of imaging techniques, we are increasingly coming across scenarios of abnormal findings on imaging. Correlation of radiographic imaging results with a thorough history and biochemical testing is essential prior to proceeding with surgical intervention.

Resume Introduction L’hyperplasie hypophysaire secondaire a une hypothyroidie peripherique reste rare et sous-diagnostiquee. Observation Un homme, âge de 18 ans, etait adresse pour prise en charge d’une masse hypophysaire. Le bilan revelait une hypothyroidie peripherique profonde et une hyperprolactinemie. L’evolution etait rapidement favorable sous l -thyroxine avec normalisation de la TSH ainsi que de la prolactinemie et disparition de la masse hypophysaire. Conclusion L’hyperplasie hypophysaire thyreotrope secondaire a l’hypothyroidie peripherique, bien que rare, doit etre reconnue afin d’eviter au patient un geste chirurgical inutile et a risque.

Hashimoto's thyroiditis is a well-known cause of growth retardation in adolescence. It is less frequently seen in children and rarely seen in infants. A 4-year-old girl was referred to our clinic for a second opinion before starting growth hormone (GH) treatment. Linear growth had markedly declined in the past 2 years, with height -3.4 standard deviations. GH deficiency was complete. She had dry, gray-sallow skin and bloated abdomen, but no goiter. The parents reported fatigue and constipation. Hormonal evaluation revealed TSH 629.5 mIU/ml, free T4 0.08 ng/dl, and prolactin 17.2 ng/ml. Bone age was 2 years. Antibodies to thyroglobulin and thyroid peroxidase were positive, suggesting Hashimoto's thyroiditis. Brain magnetic resonance imaging showed anterior pituitary hyperplasia. After 3 years of L-thyroxine therapy, she was symptomless, her height was -0.6 standard deviations, and the TSH level was normal. Brain magnetic resonance imaging showed regression of the pituitary hyperplasia.This report describes a patient with Hashimoto's thyroiditis and pituitary hyperplasia, both quite rare in very young children. Acquired hypothyroidism may appear after neonatal screening and therefore should not be overlooked in investigations of short stature, even when clinical signs of hypothyroidism are absent.• Hashimoto's thyroiditis and pituitary hyperplasia are rare in very young children. • Acquired hypothyroidism can appear after negative neonatal screening and should not be overlooked. What is New: • Short children should be evaluated for growth hormone deficiency but only after excluding other causes, particularly hypothyroidism, as we report a child with this disease but no clinical signs of it.

A 24-year-old Caucasian female patient was referred to our endocrinology service to investigate a structural magnetic resonance imaging (sMRI) finding of "pituitary mass". The first two sMRI were identified as pituitary adenoma but the following two examinations suggested the possibility of pituitary hyperplasia (PH). The patient was referred to our service for diagnostic clarification and therapy due to the divergence in sMRI reports and the surgical procedure indicated by the neurosurgical team of the other institution. The patient had no complaints, laboratory tests were all normal, and the sMRI clearly showed a PH. However, what caught our attention was her behavior. During the interview she was intermittently talking and acting like a child even though her age was 24. She reported being a foster child and was severely mistreated during childhood. Parallel psychiatric evaluation was requested and an association between the PH and the childhood abuse was identified. Early life stress may be associated with accelerated pituitary gland volume development, but there is still a paucity of data in literature about this issue. We should be aware of other cases like this one, and a correct differential diagnosis may contribute to contraindicate transsphenoidal surgery. When a childhood abuse history is present, we recommend admission to a psychiatric facility for adequate treatment.

Patients with familial isolated pituitary adenoma are predisposed to pituitary adenomas, which in a subset of cases is due to germline inactivating mutations of the aryl hydrocarbon receptor–interacting protein (AIP) gene. Using Cre/lox and Flp/Frt technology, a conditional mouse model was generated to examine the loss of the mouse homolog, Aip, in pituitary somatotrophs. By 40 weeks of age, >80% of somatotroph specific Aip knockout mice develop growth hormone (GH) secreting adenomas. The formation of adenomas results in physiologic effects recapitulating the human syndrome of acromegaly, including increased body size, elevated serum GH and insulin-like growth factor 1 levels, and glucose intolerance. The pretumorigenic Aip-deficient somatotrophs secrete excess GH and exhibit pathologic hyperplasia associated with cytosolic compartmentalization of the cyclin-dependent kinase (CDK) inhibitor p27kip1 and perinuclear accentuation of CDK-4. Following tumor formation, the Aip-deficient somatotrophs display reduced expression of somatostatin receptor subtype 5 with impaired response to octreotide. The delayed tumor emergence, even with loss of both copies of Aip, implies that additional somatic events are required for adenoma formation. These findings suggest that pituitary hyperplasia precedes adenomatous transformation in somatotroph-specific Aip-deficient mice and reveal potential mechanisms involved in the pretumorigenic state that ultimately contribute to transformation., Somatotroph-specific Aip-deficient mice displayed tumorigenic cascades of pituitary gland, accompanying with clinical features of acromegaly.

Objective To describe a patient who developed a thyrotropin (TSH)-Secreting adenoma in the setting of primary hypothyroidism. Methods We report the clinical, laboratory, and radiologic findings of a patient with a history of primary hypothyroidism who presented with headache, a bitemporal visual field deficit, and elevated TSH despite long-term levothyroxine therapy. We discuss the diagnostic challenges of this case and review the relevant literature. Results A 54-yearold woman with a history of primary hypothyroidism presented with a 3-year history of headache and a week of worsening vision. Imaging revealed a heterogeneous sellar mass elevating the optic chiasm. Her serum TSH was 46.5 mIU/L and free thyroxine concentration was 0.1 ng/dL. The differential diagnosis included pituitary hyperplasia and a TSH-secreting adenoma in a patient with primary hypothyroidism. The pathologic characteristics of the tumor were consistent with the latter. Conclusion In a patient with an elevated TSH concentration and a previous diagnosis of hypothyroidism, it is important to consider other entities besides medication noncompliance. TSH-secreting adenomas can also cause elevated levels of TSH. (Endocr Pract. 2011;17: e135-e139)

A small sella turcica is a normal anatomical variant responsible for an inadequacy between the sellar volume and its content, with a resultant bulging of the pituitary gland. It can mimic a pathological enlargement of the pituitary gland and, if not recognized, can lead to a false diagnosis of “pituitary hyperplasia” or even pituitary tumor. This is particularly true in teenage females with physiological enlargement of the pituitary gland.

Pituitary hyperplasia secondary to primary longstanding hypothyroidism has been reported in the literature in adults and rarely in children.Here we present the clinical presentation and diagnostic procedures in eight children with pituitary hyperplasia due to autoimmune thyroiditis, highlighting common findings, such as growth delay, fatigue or gaining weight, but also exceptional findings such as pericardial effusion, rhabdomyolysis, isolated hypertrichosis, and Van Wyk-Grumbach syndrome, which have rarely or never been described.Surprisingly no thyroid enlargement was detected. We discuss the unusual presenting signs of autoimmune thyroiditis that should raise the suspicion of pituitary hyperplasia. We suggest that a more elaborate clinical assessment and even modification of the diagnostic approach to autoimmune thyroiditis is needed in order to avoid its serious complications.

Pituitary hyperplasia with hyperprolactinemia has been described as a rare presentation of primary hypothyroidism. A 12-y-old child presented with intermittent headache, easy fatigability, coarseness of facial features, and hoarseness of voice for 6 mo duration. Brain imaging findings showed pituitary hyperplasia; hormonal assessment revealed primary hypothyroidism and hyperprolactinemia. Pituitary hyperplasia regressed with thyroid hormone replacement therapy. This report describes an unusual case of pituitary hyperplasia with hyperprolactinemia secondary to primary hypothyroidism.

Mutations in the prophet of PIT1 gene (PROP1) are the most common cause of multiple pituitary hormone deficiency in humans; however, the mechanism of PROP1 action is not well understood. We report that Prop1 is essential for dorsally restricted expression of a Groucho-related gene, transducin-like enhancer of split 3 (Tle3), which encodes a transcriptional corepressor. Deficiency of a related gene, amino terminal enhancer of split (Aes), causes pituitary anomalies and growth insufficiency. TLE3 and AES have been shown to interact with TCF/LEF (transcripiton factors of the T cell-specific and lymphoid enhancer specific group) family members in cell culture systems. In the absence of TCF4 (Tcf7L2), Prop1 levels are elevated, pituitary hyperplasia ensues and palate closure is abnormal. Thus, we demonstrate that Tcf4 and Aes influence pituitary growth and development, and place Tcf4 and Tle3 in the genetic hierarchy with Prop1.

GERIATRIC retired horses are frequently kept by their owners as a companion for their current riding horse or simply as a much loved 9lawnmower9. With age, horses experience specific clinical problems, including osteoarthritis (degenerative joint disease), weight loss, pituitary hyperplasia and related conditions. These common causes of debility in the older horse are often insidious in onset and usually progressive but, when managed appropriately, animals can maintain a reasonable quality of life. This article discusses the diagnosis and clinical management of these conditions in the older horse and pony.

Long-standing hypothyroidism causing thyrotroph hyperplasia can result in enlargement of the pituitary gland and hyperprolactinemia. A 20-year-old unmarried girl presented with galactorrhea for 4 months. She was evaluated and diagnosed to have severe hypothyroidism resulting in hyperprolactinemia and reversible pituitary hyperplasia. This case helps the clinicians to be aware of an unusual presentation of severe primary hypothyroidism and reminds to consider it in the differential diagnosis of pituitary enlargement with mild hyperprolactinemia.

Limited data are available on pituitary gigantism, as it is a rare disorder. This study was carried out to assess the clinical, hormonal, and radiologic profiles and management outcomes of patients with pituitary gigantism.We conduced a retrospective analysis of 14 patients with pituitary gigantism who presented to a single tertiary care institute from 1990 to 2014.Thirteen patients were male, and 1 was female. The mean age at diagnosis was 21.9 ± 6.1 years, with a mean lag period of 6.5 ± 5.6 years. The mean height SD score at the time of diagnosis was 3.2 ± 0.6. Symptoms of tumor mass effect were the chief presenting complaint in the majority (50%) of patients, while 2 patients were asymptomatic. Six patients had hyperprolactinemia. At presentation, the nadir PGGH (postglucose GH) and insulin-like growth factor (IGF 1)-ULN (× upper limit of normal) were 63.2 ± 94.9 ng/mL and 1.98 ± 0.5, respectively. All (except 1 with mild pituitary hyperplasia) had pituitary macroadenoma. Six patients had invasive pituitary adenoma. Transsphenoidal surgery (TSS) was the primary modality of treatment in 13/14 patients, and it achieved remission in 4/13 (30.76%) patients without recurrence over a median follow-up of 7 years. Post-TSS radiotherapy (RT) achieved remission in 3/5 (60%) patients over a median follow-up of 3.5 years. None of the patients received medical management at any point of time.Gigantism is more common in males, and remission can be achieved in the majority of the patients with the help of multimodality treatment (TSS and RT).

Pituitary thyrotroph hyperplasia secondary to primary hypothyroidism is a rare cause of pituitary enlargement. We report a case of pituitary hyperplasia in a young woman thought to have a pituitary macroadenoma with suprasellar extension. A 21-year-old woman was admitted to our hospital, complaining of menstrual irregularity and galactorrhea. Serum thyrotropin and prolactin were high, and serum-free thyroxine was low. Magnetic resonance imaging revealed symmetrical pituitary enlargement associated with contrast enhancement simulating macroadenoma. After adequate hormone replacement therapy with levothyroxine, both symptoms and pituitary hyperplasia regressed within 4 months. It is concluded that pituitary tumor associated with elevated thyroid stimulating hormone and low levels of free T4 should always be treated with replacement thyroxine before other diagnostic tests are ordered.

The development of pituitary tumours as a consequence of primary target organ failure is rare. We report here a rare case of pituitary hyperplasia with suprasellar extension due to primary myxoedema. This case presentation suggested the importance of detailed endocrine investigation and repeated magnetic resonance imaging for the differential diagnosis of pituitary enlargement to avoid unnecessary surgery.

We present the first case of iatrogenic hypothyroidism as a result of compounded thyroid hormone (T4/T3) therapy. The thyroid replacement was changed from 175 µg levothyroxine (LT4) to 57/13.5 µg compounded T4/T3 daily in order to improve the T3 level, despite normal thyroid-stimulating hormone (TSH). This resulted in clinical manifestations of hypothyroidism and high TSH level (150 µIU/mL). Six months later, the patient was referred to our clinic for abnormal pituitary magnetic resonance imaging. On reinitiating a physiologic dose of LT4, clinical and biochemical abnormalities resolved and the pituitary gland size decreased. Our case emphasizes the importance of using TSH level to gauge dose adjustments in primary hypothyroidism. Also, it underscores the current American Thyroid Association recommendation against routine use of compounded thyroid hormone therapy.

Endocrinology and Diabetology Unit (E.P., A.T., B.A., S.C.), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Policlinico San Donato, 20097 San Donato Milanese, Milan, Italy; Department of Medical-Surgical Sciences (E.P., B.A., S.C.), University of Milan, 20097 San Donato Milanese, Milan, Italy; Department of Neurosurgery (M.L.), IRCCS Fondazione Ca’ Granda Policlinico, 20122 Milano, Milan, Italy; and Endocrinology Unit (A.G.L.), Department of Medical Sciences, University of Milan, IRCCS Fondazione Ca’ Granda Policlinico, 20122 Milan, Italy

We describe a15-year-old girl presenting with compensatory pituitary enlargement due to primary hypothyroidism. The hyperplasia regressed following thyroxine administration. The clinical, laboratory and MRI features of the patients are described and the mechanisms of pituitary gland enlargement are discussed.

Pituitary hyperplasia is generally associated with end-organ failure such as primary hypothyroidism, physiological changes such as puberty and pregnancy, or neoplasms secreting releasing factors. We present a full-term infant with an enlarged pituitary height of 8 mm at age 3 days despite a normal endocrinological evaluation. Repeat imaging at 5 months of age revealed a normal-size pituitary gland. To our knowledge, pituitary hyperplasia has not been described in a neonate with normal pituitary function.

We present eight cases with short stature, pituitary hyperplasia, and hypothyroidism. Pituitary hyperplasia due to primary hypothyroidism was diagnosed on the basis of clinical manifestations, endocrine examination and MRI. After 2 to 6 months of L-thyroxine replacement therapy, the signs of hypothyroidism disappeared; free triiodothyronine, free thyroxine, thyrotropin and prolactin became normal; and pituitary enlargement regressed. In two children, the growth rate remained low when treated with L-thyroxine, but with additional recombinant human growth hormone (rhGH), the height increased by 11 cm per year. No recurrence of lesions was found on follow-up.

Pituitary hyperplasia secondary to primary hypothyroidism has been reported in the literature in both adults and children. We report a case of a young woman who was diagnosed with hypothyroidism in her teenage years. Despite frequent follow-up, her TSH levels remained greater than 100 mIU/ml. A few years later, pituitary enlargement was found on an MRI at a time when her TSH was 177 mIU/ml and her free T4 was 0.2 ng/dl. Observed administration of 600 mcg of L-thyroxine was performed to determine the effectiveness of hormone absorption. Total T4 levels of 0.2 rose to 7.1 mcg/dl at two hours with a decrease in her TSH levels from 88.6 to 66.8 mIU/ml at 24 hours. With the exception of one short period, her TSH levels have remained elevated over eight years of observation without change in the size of the pituitary mass. In our review of the literature, primary uncontrolled hypothyroidism has been described as a precursor to pituitary hyperplasia. In these patients, TSH-secreting adenomas were distinguished from pituitary hyperplasia by a blunted TRH stimulation test, elevated alpha subunit concentration values, and elevated alpha subunit concentration/TSH ratios. TSH levels ranged from 98 to 732 mIU/ml in adults, and even higher values in children. Following adequate hormone replacement with L-thyroxine doses of 25 to 300 mcg/day, both symptoms and pituitary hyperplasia regressed on average within a few months.

An eight-year, 4-month old Indian girl with low IQ and delayed milestones, presented with headache (4 years), breast development (4 months), and menstrual bleeding for 22 days. Examination revealed short stature [height: 91.5 cm; SD score: -5.59], coarse dry skin, umbilical hernia (arrow), delayed reflexes, Tanner’s stage-3 breasts, absent pubic and axillary hair

Reactive enlargement of the pituitary gland in primary end organ failure may be indistinguishable from primary pituitary lesions in clinical presentation and on magnetic resonance imaging. The diagnosis of pituitary hyperplasia secondary to end organ failure must be based on endocrinologic investigations. Recognition of this condition and distinguishing it from primary pituitary tumors is important and may eliminate unnecessary surgery.

This review emphasizes emerging concepts in regulation of the hypothalamicpituitary-adrenal (HPA) axis. We first discuss relevant physiologic pathways and molecular mechanisms that control the HPA axis. Imbalances at many levels can disrupt HPA axis homeostasis leading to conditions such as Cushing’s syndrome, pituitary hyperplasia, and anxiety disorders. We then describe recently developed animal models with specific alterations in corticotropin pathways. The primary elements of these pathways have been engineered for upregulation, downregulation or deficiency and thus provide a powerful collection of models for studying HPA axis regulation. These models provide new views into features critical for maintaining control of the HPA axis. They have expanded our understanding of the degree of plasticity and compensation that exists within this system. In addition, they reveal novel mechanisms whereby inappropriate or absent regulatory components lead to abnormal endocrine manifestations and behavioral states.

A 23 year old man presented with classical hypothyroidism of 9 years duration. This was associated with pituitary enlargement, documented on magnetic resonance imaging (MRI), and abnormal half-field visual evoked responses (VERs). Following the initiation of thyroxine therapy the pituitary enlargement and the VER abnormalities resolved. The final diagnosis was of primary hypothyroidism with secondary pituitary hyperplasia.

Pituitary hyperplasia consequent to untreated primary hypothyroidism undergoes impressive regression following thyroxine therapy. We describe a young man with primary hypothyroidism and pituitary hyperplasia, who showed significant but incomplete regression of pituitary enlargement despite 18 months of L-thyroxine therapy (1 year in replacement dose (150 micrograms/day) and an additional 6 months in suppressive dose (300 micrograms/day)).

Magnetic resonance imaging of pituitary hyperplasia has been rarely described in children with primary hypothyroidism. We report a case of pituitary hyperplasia in a child presented with significant growth arrest and laboratory evidence of hypothyroidism. Magnetic resonance imaging revealed symmetrical pituitary enlargement simulating macroadenoma. After thyroid hormone replacement therapy, the child's height increased and pituitary enlargement regressed to normal. Awareness of MRI appearance of pituitary hyperplasia in children with laboratory evidence of hypothyroidism might avoid misdiagnosis for pituitary tumor, which may also manifest as growth disorder, obviating unnecessary surgery.