Impaired insulin sensitivity (IS) and β-cell dysfunction result in hyperglycaemia in patients of acromegaly. However, alterations in incretins and their impact on glucose-insulin homeostasis in these patients still remain elusive. Twenty patients of active acromegaly (10 each, with and without diabetes) underwent hyperinsulinemic euglycaemic clamp and mixed meal test, before and after surgery, to measure indices of IS, β-cell function, GIP, GLP-1 and glucagon response. Immunohistochemistry (IHC) for GIP and GLP-1 was also done on intestinal biopsies of all acromegalics and healthy controls. Patients of acromegaly, irrespective of presence or absence of hyperglycaemia, had similar degree of insulin resistance, however patients with diabetes exhibited hyperglucagonemia, and compromised β-cell function despite significantly higher GIP levels. After surgery, indices of IS improved, GIP and glucagon levels decreased significantly in both the groups, while there was no significant change in indices of β-cell function in those with hyperglycaemia. IHC positivity for GIP, but not GLP-1, staining cells in duodenum and colon was significantly lower in acromegalics with diabetes as compared to healthy controls possibly because of high K-cell turnover. Chronic GH excess induces an equipoise insulin resistance in patients of acromegaly irrespective of their glycaemic status. Dysglycaemia in these patients is an outcome of β-cell dysfunction consequent to GIP resistance and hyperglucagonemia.

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DesCripTionA 57-year-old female presented with history of rapidly progressing multiple swellings over her face, forehead and sternum for the last 6 months (figure 1). On examination, these swellings were non-tender and hard in consistency. Her thyroid gland was not palpable. Thyroid function tests were normal. FNAC (Fine needle aspiration cytology) from the bony swelling revealed metastatic follicular thyroid carcinoma (FTC) (figure 2) with thyroglobulin (Tg) positivity on immunohistochemistry. Ultrasonography of the neck revealed a normal-sized thyroid gland with multiple hypoechoeic lesions and calcification. FDG-PET (Fluorodeoxyglucose -positron emission tomography) displayed diffuse osseous metastasis. She underwent total thyroidectomy, and histopathology was consistent with FTC. Postoperatively, serum Tg was 552 ng/mL (normal 1.4-78 ng/mL) and anti-Tg antibody was 15 IU/mL (normal <60 IU/mL). She also received zoledronic acid and high dose radioiodine ablation with scan showing a faint tracer uptake by the metastatic lesions. The patient was lost to follow-up and died a year after she presented first.Malignancies associated with a tendency to metastasize to flat bones include thyroid, breast and prostate carcinoma. Thyroid malignancy is rare and accounts for only 2% of all solid malignancies. FTC occurs in older people, the mean age at diagnosis being 50 years. Painless thyroid nodule is the most common presenting manifestation, while 1%-9% present with distant metastasis, as seen in our patient. The lung (50%) and bone (25%) are the most common sites of distant metastasis and bony lesions are mostly osteolytic.1 More than 80% of bone metastases from thyroid malignancies are located in the red marrow of the axial skeleton, where blood flow is high (eg, vertebrae, ribs and hips) and a conducive milieu exists for tumour growth due to the presence of growth factors, such as IGF-1 (Insulin-like growth factor-1) and IGF-2 (Insulin-like growth factor-2, FGFs (Fibroblast growth factors) and PDGFs (Platelet derived growth factors).2 Thyroid carcinoma with distant metastasis is associated with poor prognosis with 10-year survival rate of 40%. 3 Learning points► Follicular thyroid carcinoma presenting with bony metastasis is quite uncommon. ► Presence of bony metastasis in FTC is associated with poor prognosis. ► Majority of the bony metastasis in FTC involve vertebrae, ribs and pelvic bones; however, skull involvement is not very frequent. ► Lenvatinib, an oral multitargeted tyrosine kinase inhibitor, is an effective therapeutic alternative in radioiodine refractory metastases.Contributors VSS prepared and edited the manuscript. AB diagnosed and managed the case and also edited the manuscript.Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.Competing interests None declared.

DescriptionA 31-year-old woman presented with a history of bone pains, difficulty in walking and painless swelling of the left foot for the last 1 year (figure 1). X-ray of the left foot showed multiple lytic lesions in metatarsal bones and the absence of proximal half of shaft of second metatarsal. Biochemistry results revealed corrected serum calcium 11.2 mg/ dL, phosphate 2.0 mg/dL, alkaline phosphatase 1049 IU/mL, intact parathyroid hormone (iPTH) 2543 pg/mL, 25-hydroxyvitamin D 16.2 ng/mL, and serum creatinine 0.6 mg/dL. She had no history of pancreatitis or evidence of renal/gall stone disease. The skeletal survey showed multiple osteitis fibrosa cystica (OFC) lesions, pathological fracture of shaft of the left femur and salt and pepper appearance of the skull (figure 2a, b, c). Sestamibi scan revealed right inferior parathyroid adenoma measuring 3.0×2.9×2.2 cm. Based on the above findings, a diagnosis of primary hyperparathyroidism (PHPT) was made and she underwent parathyroid adenectomy. Tumour weighed 4 g and histopathology was consistent with clear cell parathyroid adenoma.The classic bone disease of PHPT, OFC is seen in <2% of patients.1 In severe and long-standing disease, elevated PTH causes increased osteoclast activity resulting in localised alterations in the trabecular pattern, demineralisation and replacement of marrow by loose connective tissue, leading to radiographic disappearance of bones, as was seen in our patient.2 They are most commonly seen in flat bones, however, metacarpals and metatarsals are very rarely involved. Differentials of vanishing bone disease besides PHPT include osteomyelitis, Charcot's neuroarthropathy, rheumatoid arthritis, osseous metastasis and Gorham's disease.contributors VSS: managed the case and prepared the manuscript. AB: conceived the idea and edited the manuscript. Learning points► Primary hyperparathyroidism should be considered in the differential diagnosis of vanishing bone disease. ► 'Osteitis fibrosa cystica' is rare and represents severe form of bone disease in primary hyperparathyroidism.