Search

Purpose To assess the distribution of clinical features and metabolic abnormalities of polycystic ovary syndrome (PCOS) women according to their age. Methods Retrospective study on 602 women (mean age 23.9 ± 6.2 years), diagnosed according to International PCOS Network Guidelines criteria as having PCOS in a University-based Hospital. Anthropometric features, hormonal and metabolic parameters were measured and compared between the different age groups (group A ≤ 20 years; group B 21–30 years; group C > 30 years). Results Patients in group A were more often hyperandrogenic, while in group C hypertension, dyslipidemia, obesity, impaired fasting glucose, and insulin resistance (IR) were more prevalent. After adjusting for BMI, age correlated positively with sex hormone-binding globulin (SHBG), IR, total- and LDL-cholesterol, and negatively with DHEAS, insulin, and free androgen index (FAI). SHBG was significantly associated with IR and atherogenic dyslipidemia, while FAI levels were linked to hypertension, independently of other factors considered. Furthermore, the regression analysis showed a stronger relationship between BMI and metabolic outcomes, regardless of age. Conclusion Polycystic ovarian syndrome (PCOS) phenotype changes with age. Clinical and biochemical hyperandrogenism are a major concern in young PCOS women, while metabolic burden tends to increase with aging. Some of the cardiovascular risk factors are dependent on FAI and SHBG levels, whereas BMI confirms its key role in the genesis of most of the metabolic sequelae in PCOS, independently of age.

Part 2 of this series of Continuing Education articles on benign thyroid disorders deals with nodular goiter, hypothyroidism, and subacute thyroiditis. Together with Part 1 (which dealt with various forms of hyperthyroidism), this article is intended to provide relevant information for specialists in nuclear medicine dealing with the clinical management of patients with benign thyroid disorders, the primary audience for this series. Goiter, an enlargement of the thyroid gland, is a common endocrine abnormality. Constitutional factors, genetic abnormalities, or dietary and environmental factors may contribute to the development of nodular goiter. Most patients with nontoxic nodular goiter are asymptomatic or have only mild mechanical symptoms (globus pharyngis). Work-up of these patients includes measurement of thyroid-stimulating hormone, free triiodothyronine, free thyroxine, thyroid autoantibodies, ultrasound imaging, thyroid scintigraphy, and fine-needle aspiration biopsy of nodules with certain ultrasound and scintigraphic features. Treatment for multinodular goiter includes dietary iodine supplementation, surgery, radioiodine therapy (to decrease thyroid size), and minimally invasive ablation techniques. Hypothyroidism ranges from rare cases of myxedema to more common mild forms (subclinical hypothyroidism). Primary hypothyroidism often has an autoimmune etiology. Clinical presentations differ in neonates, children, adults, and elderly patients. Work-up includes thyroid function tests and ultrasound imaging. Nuclear medicine is primarily used to locate ectopic thyroid tissue in congenital hypothyroidism or to detect defects in iodine organification with the perchlorate discharge test. Treatment consists of thyroid replacement therapy with l-thyroxine, adjusting the daily dose to the individual patient’s metabolic and hormonal requirements. Subacute thyroiditis is a self-limited inflammatory disorder of the thyroid gland, often associated with painless or painful swelling of the gland and somatic signs or symptoms. Inflammation disrupts thyroid follicles resulting in a rapid release of stored thyroxine and triiodothyronine causing an initial thyrotoxic phase, often followed by transient or permanent hypothyroidism. Although subacute thyroiditis is often related to a viral infection, no infective agent has been identified. Subacute thyroiditis may be caused by a viral infection in genetically predisposed individuals. Work-up includes lab tests, ultrasound imaging, and radionuclide imaging. Thyroid scintigraphy demonstrates different findings depending on the phase of the illness, ranging from very low or absent tracer uptake in the thyroid gland in the hyperthyroid phase to a normal appearance in the late recovery phase. Since subacute thyroiditis is self-limited, treatment is directed toward relief of pain. High-dose nonsteroidal antiinflammatory drugs are usually the first-line treatment. If severe pain persists, a course of corticosteroids may be necessary. Permanent hypothyroidism develops in up to 15% of patients with subacute thyroiditis, even more than 1 y after presentation.

Nonautoimmune subclinical hypothyroidism (NSH) is characterized by elevated serum TSH in presence of normal thyroid hormone levels and absence of anti-thyroid antibodies. As result of a genomic-wide study, a strong association between three polymorphic variants in intron 1 of human PDE8B gene (rs4704397, rs6885099, rs2046045) and serum TSH has been reported in euthyroid subjects.The aim of this study was to evaluate frequency and effects on serum TSH of PDE8B gene polymorphisms in patients with sporadic NSH and verify if differences in serum TSH levels are associated to these polymorphic variants.A total of 58 Italian selected patients affected by NSH, with elevated serum TSH, normal FT3 and FT4 and without TSHr gene mutations, were subjected to genotyping for specific single nucleotide polymorphism of PDE8B gene.In all patients, the integrity of TSH receptor gene was attested. The ancestral allele associated with increased serum TSH was present in 42/58 patients (72.4 %) for rs4704397, in 42/58 patients (72.4 %) for rs6885099 and in 44/58 patients (75.9 %) for rs2046045. However, similar values of serum TSH were detected in patients with minor or major allele for each polymorphism.A prevalence of the minor allele of PDE8B gene polymorphism associated with elevated serum levels of TSH was demonstrated in patients affected by sporadic NSH; however, significant differences in circulating TSH in patients with minor or major alleles for each polymorphism were not identified demonstrating the lack of association between the polymorphisms and serum TSH levels in these patients.

Congenital hypothyroidism (CH) due to thyroglobulin (TG) deficit is an autosomal recessive disease (OMIM #274700) characterized by hypothyroidism, goiter, low serum TG, and a negative perchlorate discharge test. The aim of this study was to perform the genetic analysis of the TG gene in two sisters born from consanguineus parents and affected by CH and low serum TG levels. The index patient and her sister were identified at neonatal screening for CH and treated with L-thyroxine (L-T4). After discontinuation of L-T4 therapy, hypothyroidism was confirmed, serum TG was undetectable, and no organification defect after 123I scintigraphy and perchlorate test was shown; thyroid ultrasound showed a eutopic gland of normal size. DNA was extracted from peripheral white blood cells of the two sisters and the father. All 48 exons of TG gene were amplified by polymerase chain reaction and subjected to direct sequencing. A novel homozygous point mutation in exon 10 of TG gene was identified in the patient and her sister. The mutation determined a stop codon at position 768 (R768X) resulting in an early truncated protein or in the complete absence of the protein. The father (euthyroid) was heterozygous carrier of the mutation. Conclusion: Genetic analysis of TG gene was performed in two sisters affected by CH. A novel point mutation of the TG gene determining a stop codon at position 768 of the protein was identified. The early truncated nonfunctioning protein or the absence of the protein due to the premature degradation of abnormal mRNA may be responsible of the observed phenotype.

BACKGROUND: Iodide transport defects (ITDs), rare causes of congenital hypothyroidism (CH), have been shown to arise from abnormalities of the sodium/iodide symporter (NIS). We describe a 16-year-old girl with CH caused by an ITD resulting from a novel mutation of NIS. SUMMARY: A 16-year-old girl with CH diagnosed by a neonatal screening program received early treatment with L-thyroxine replacement therapy. A (123)I scan had failed to reveal any iodide uptake by the thyroid and salivary glands; thus, thyroid agenesis was diagnosed. Thyroglobulin (Tg) was not measured when she was a neonate or infant. Unexpectedly, at the age of 14.5 years, a nodular goiter and high serum Tg concentrations (303 ng/mL; normal