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Summary Conventional treatment of hypoparathyroidism relies on oral calcium and calcitriol. Challenges in managing post-parathyroid- and post-thyroidectomy hypocalcaemia in patients with a history of bariatric surgery and malabsorption have been described, but postoperative management of bariatric surgery in patients with established hypoparathyroidism has not. We report the case of a 46-year-old woman who underwent elective sleeve gastrectomy on a background of post-surgical hypoparathyroidism and hypothyroidism. Multiple gastric perforations necessitated an emergency Roux-en-Y gastric bypass. She was transferred to a tertiary ICU and remained nil orally for 4 days, whereupon her ionised calcium level was 0.78 mmol/L (1.11–1.28 mmol/L). Continuous intravenous calcium infusion was required. She remained nil orally for 6 months due to abdominal sepsis and the need for multiple debridements. Intravenous calcium gluconate 4.4 mmol 8 hourly was continued and intravenous calcitriol twice weekly was added. Euthyroidism was achieved with intravenous levothyroxine. Maintaining normocalcaemia was fraught with difficulties in a patient with pre-existing surgical hypoparathyroidism, where oral replacement was impossible. The challenges in managing hypoparathyroidism in the setting of impaired enteral absorption are discussed with analysis of the cost and availability of parenteral treatments. Learning points: Management of hypoparathyroidism is complicated when gastrointestinal absorption is impaired. Careful consideration should be given before bariatric surgery in patients with pre-existing hypoparathyroidism, due to potential difficulty in managing hypocalcaemia, which is exacerbated when complications occur. While oral treatment of hypoparathyroidism is cheap and relatively simple, available parenteral options can carry significant cost and necessitate a more complicated dosing schedule. International guidelines for the management of hypoparathyroidism recommend the use of PTH analogues where large doses of calcium and calcitriol are required, including in gastrointestinal disorders with malabsorption. Approval of subcutaneous recombinant PTH for hypoparathyroidism in Australia will alter future management.

Endothelial cells line blood vessels and modulate vascular tone, thrombosis, inflammatory responses and new vessel formation. They are implicated in many disease processes including atherosclerosis and cancer. IGFs play a significant role in the physiology of endothelial cells by promoting migration, tube formation and production of the vasodilator nitric oxide. These actions are mediated by the IGF1 and IGF2/mannose 6-phosphate receptors and are modulated by a family of high-affinity IGF binding proteins. IGFs also increase the number and function of endothelial progenitor cells, which may contribute to protection from atherosclerosis. IGFs promote angiogenesis, and dysregulation of the IGF system may contribute to this process in cancer and eye diseases including retinopathy of prematurity and diabetic retinopathy. In some situations, IGF deficiency appears to contribute to endothelial dysfunction, whereas IGF may be deleterious in others. These differences may be due to tissue-specific endothelial cell phenotypes or IGFs having distinct roles in different phases of vascular disease. Further studies are therefore required to delineate the therapeutic potential of IGF system modulation in pathogenic processes.

Thyrotoxicosis is an under-recognised but clinically important complication of parathyroidectomy. We report a case of a 37-year-old man with tertiary hyperparathyroidism who initially developed unexplained anxiety, diaphoresis, tachycardia, tremor and hyperreflexia one day after subtotal parathyroidectomy. Thyroid biochemistry revealed suppressed thyroid stimulating hormone and elevated serum free T4 and free T3 levels. Technetium-99m scintigraphy scan confirmed diffusely decreased radiotracer uptake consistent with thyroiditis. The patient was diagnosed with thyrotoxicosis resulting from palpation thyroiditis. Administration of oral beta-adrenergic antagonists alleviated his symptoms and there was biochemical evidence of resolution fourteen days later. This case illustrates the need to counsel patients about thyroiditis as one of the potential risks of parathyroid surgery. It also emphasises the need for biochemical surveillance in patients with unexplained symptoms in the post-operative period and may help to minimise further invasive investigations for diagnostic clarification. Learning points Thyroiditis as a complication of parathyroidectomy surgery is uncommon but represents an under-recognised phenomenon. It is thought to occur due to mechanical damage of thyroid follicles by vigorous palpation. Palpation of the thyroid gland may impair the physical integrity of the follicular basement membrane, with consequent development of an inflammatory response. The majority of patients are asymptomatic, however clinically significant thyrotoxicosis occurs in a minority. Patients should be advised of thyroiditis/thyrotoxicosis as a potential complication of the procedure. Testing of thyroid function should be performed if clinically indicated, particularly if adrenergic symptoms occur post-operatively with no other cause identified. Background Although thyroiditis can occur following parathyroidectomy surgery, it is not a commonly recognised clinical complication. This phenomenon has been described in the literature as ‘palpation thyroiditis’ (1). The mechanism has not been fully elucidated but several theories have been proposed. Intraoperative trauma by vigorous palpation of the gland causing rupture of isolated thyroid follicles is the most commonly postulated mechanism. The risk appears to increase with the extent of neck exploration surgery (2, 3), but palpation thyroiditis has also been described in patients undergoing surgery for primary hyperparathyroidism (4, 5). Palpation of the thyroid gland causing impairment of the physical integrity of the follicular epithelium and a subsequent inflammatory process otherwise termed ‘multifocal granulomatous folliculitis’ has also been hypothesised as a causal mechanism (4). Histologically this is characterised by an infiltrate with histiocytes, plasma cells, lymphocytes and haemosiderin-laden macrophages (6). The majority of patients with palpation thyroiditis are clinically asymptomatic and only a minority develop symptoms of overt thyrotoxicosis. The incidence of TSH suppression in clinically asymptomatic patients is much higher. Studies have reported biochemical hyperthyroidism, defined as full TSH suppression, occurring after parathyroidectomy in as many as 31–42% of patients, whereas only ~15% are symptomatic (5). The variability in incidence rates may be accounted for by (i) the primary indication for surgery; (ii) varying operative techniques used for primary, secondary and tertiary hyperparathyroidism; (iii) the extent of intraoperative gland manipulation; and (iv) variations in thyroid shape, size and pre-operative function (5). Abnormal values of TSH, free T4 (fT4) and free T3 (fT3) indicating post-operative thyrotoxicosis are observed in patients with palpation thyroiditis. The levels of fT4 and fT3 usually reach their maximum on post-operative day 1–3, whereas the TSH nadir occurs around post-operative day 5 (5). Thyroglobulin released from the injured thyroid follicles also increases, and has been suggested as a suitable marker supporting the diagnosis. Thyroglobulin levels greater than 90ng/mL are suggestive of post-operative palpation thyroiditis (5). Spontaneous resolution can be expected by 6weeks in the vast majority of patients given that the half-life of fT4 is one week (i.e. 5–6 half-lives until resolution) (3). Persistence thereafter should prompt the clinician to search for an alternative cause of hyperthyroidism. We report a case of a patient who underwent subtotal parathyroidectomy for tertiary hyperparathyroidism, which was complicated by thyroiditis causing symptomatic thyrotoxicosis. This is the first published case report of such early thyrotoxicosis as supported by a TSH nadir by day 5 post-operatively and absence of tracer uptake on a Tc-99m pertechnetate thyroid scan.

Insulin-like growth factors IGF-I and IGF -II are important mediators of growth. A family of six high affinity IGF binding proteins (IGFBPs) modulate IGF action. IGFBPs have three domains, of which the N- and C-domains are involved in high affinity IGF binding. IGFBP-6 is unique in its 20-100-fold IGF-II binding specificity over IGF-I. The aim of this study was to determine the contributions of the N- and C-domains of IGFBP-6 to its IGF binding properties. We confirmed that differential dissociation kinetics are responsible for the IGF-II binding preference of IGFBP-6. The N-domain has rapid association kinetics, similar to full-length IGFBP-6, but both IGF-I and -II dissociate rapidly from this domain, thereby reducing its binding affinity for IGF-II approximately 50-fold. However, the N-domain binds IGF-I and -II with similar affinities and it has a similar IGF-I binding affinity to full-length IGFBP-6. This suggests that the C-domain confers the IGF-II binding preference of IGFBP-6; indeed, IGF-I bound inconsistently with very low affinity to the C-domain. Coincubation studies showed that isolated N- and C-domains of IGFBP-6 do not strongly cooperate to enhance IGF binding. The results of the binding studies are supported by the effects of the IGFBP-6 domains on IGF-induced colon cancer cell proliferation; the N-domain inhibited IGF-II induced proliferation with approximately 20-fold lower potency than IGFBP-6 and it was equipotent in inhibiting IGF-I- and IGF-II-induced proliferation. Coincubation of C-domain had no additional effect on N-domain-induced inhibition of proliferation. In conclusion, both the N- and C-domains of IGFBP-6 are involved in IGF binding, the C-domain is responsible for the IGF-II binding preference of IGFBP-6 and intact IGFBP-6 is necessary for high affinity IGF binding.

PC12 rat phaeochromocytoma cells are widely used as a model of neuronal differentiation. They express IGF receptors and are responsive to IGFs. The main IGF-binding protein synthesized by these cells is IGFBP-6. Glucocorticoids induce differentiation of PC12 cells towards a chromaffin phenotype. The effect of dexamethasone on IGFBP-6 levels was therefore studied. Dexamethasone (500 nM) decreased IGFBP-6 protein in conditioned media and mRNA levels to 61 +/- 5% (P < 0.0001) and 34 +/- 14% (P = 0.03) of control levels respectively. Incubation of PC12 cells with IGF-II (100 ng/ml) for 72 h increased IGFBP-6 protein levels in media to 217 +/- 19% of control (P < 0.0001). IGFBP-6 mRNA levels, however, were unchanged. IGF-I had similar effects on IGFBP-6 protein and mRNA levels. IGFs increased cell number by 50-60%, but this was insufficient to explain the increases in protein levels. IGFBP-6 was not released from a cell-associated reservoir or protected from proteolysis by IGFs, excluding these post-translational mechanisms as explanations for the IGF effects on IGFBP-6 levels. The effects of IGF-II and dexamethasone on IGFBP-6 levels were independent. These results indicated that (1) dexamethasone decrease IGFBP-6 at the mRNA level, and (2) IGFs stimulate IGFBP-6 levels by a post-transcriptional mechanism.