Amar Agha

Context: Primary hyperparathyroidism occurs in almost all patients with the syndrome of multiple endocrine neoplasia type 1 (MEN1), but the association of MEN1 with parathyroid carcinoma has only been described previously in a single patient. In this report, we describe two further cases of parathyroid carcinoma presenting in MEN1 syndrome. Case reports: The first patient was a 69-yr-old woman, who presented with severe primary hyperparathyroidism and tracheal compression by a large mediastinal mass, which was shown histologically to be a parathyroid carcinoma with a second similar lesion in the neck. She was treated with total parathyroidectomy followed by resection of the mediastinal mass with resolution of the hypercalemia. Remarkably, she also reported primary amenorrhea and was found to have an invasive pituitary lactotroph adenoma, which was treated with cabergoline and external beam radiotherapy. Magnetic resonance imaging (MRI) of the pancreas revealed a small lesion characteristic of an islet-cell tumor, which was clinically and biochemically non-functioning. The second patient was a 32-yr-old man who presented with symptomatic hypercalemia and markedly raised serum PTH concentration. Neck exploration revealed two parathyroid glands only. One of the parathyroid glands contained a tumor with fibrous banding, atypical mitoses, extra-capsular extension and moderate Ki 67 staining; features which are highly suggestive of carcinoma. He also had intractable dyspepsia associated with raised serum gastrin concentration. A lesion was localized to the neck of the pancreas by endocopic ultrasound, and a selective arterial calcium stimulation catheter suggested the presence of both a gastrinoma and an insulinoma, although he had no hypoglycemic symptoms. Pituitary MRI was normal. The patient’s mother had primary hyperparathyroidism. Conclusions: This case report describes two further patients in whom parathyroid carcinomas occurred in the context of MEN1, which gives a new insight to the possible presenting phenotype of this condition. Both patients had negative genetic screening for classic MEN1 gene mutation, which may suggest that one or more novel occult mutations may be responsible for this aggressive phenotype.

Summary: Traumatic brain injury (TBI) is the commonest cause of death and disability in young adults living in industrialized countries. Several recent studies have convincingly shown that anterior hypopituitarism is a common complication of head trauma with a prevalence of at least 25% among long‐term survivors. This is a much higher frequency than previously thought and suggests that most cases of post‐traumatic hypopituitarism (PTHP) remain undiagnosed and untreated. These findings raise important questions about the potential contribution of PTHP to the high physical and neuropsychiatric morbidity seen in this group of patients. In this review, we examine the published reports on the neuroendocrine abnormalities in TBI patients and highlight new data that give novel insights into the natural history of this disorder. We discuss the potential contribution of PTHP to recovery and rehabilitation after injury and the need for the identification and the appropriate and timely management of hormone deficiencies to optimize patient recovery from head trauma, improve quality of life and avoid the long‐term adverse consequences of untreated hypopituitarism.

Context: Hypothalamic-pituitary (HP) dysfunction is common in children treated with cranial radiotherapy (RT) for brain tumors, but there is little known about the risk of HP dysfunction in adults treated with RT for primary nonpituitary brain tumors. Objective: The objective was to study the frequency of HP dysfunction in adults after RT for nonpituitary brain tumors. Method: We studied 56 adult patients who received external beam RT for primary nonpituitary brain tumors at time intervals of 12–150 months after RT. The control group consisted of 20 RT-naive patients with primary brain tumors. GH and adrenal axes were assessed using the insulin tolerance test or the glucagon stimulation test. Gonadotroph, thyrotroph, and lactotroph function were assessed using baseline blood measurements. The biological effective dose (BED) to the HP axis was calculated in the RT patients. Results: Hypopituitarism was present in 41% of patients. The frequency of GH, ACTH, gonadotropin, and TSH deficiencies, and hyperprolactinemia was 32, 21, 27, 9, and 32%, respectively. Any degree of hypopituitarism and GH deficiency was significantly associated with longer time interval from RT and greater BED. However, gonadotropin deficiency and hyperprolactinemia were only related to BED, whereas ACTH deficiency was only significantly associated with the time interval from RT. One RT-naive patient was GH deficient. Conclusion: Adult patients treated with cranial irradiation for primary nonpituitary brain tumors are at high risk of hypopituitarism, which is time and dose dependent. Long-term surveillance and periodic evaluation are needed. We recommend that adult late effect clinics, similar to those for children, should be established.

Small-cell lung cancer presenting with a combination of cranial diabetes insipidus and Cushing's syndrome secondary to ectopic adrenocorticotropin (ACTH) secretion is very rare and has only been described previously in one case report Our patient was a 49 year old man, in whom the initial presenting features of small-cell lung cancer were cranial diabetes insipidus secondary to pituitary metastases and severe hypokalaemia resulting from ectopic ACTH hormone secretion. This case is a remarkable example of the complex metabolic endocrine manifestations of small-cell lung cancer.

Background Target blood pressure control in patients with type 2 diabetes should be 130/85mmHg or less; however, it is not clear how achievable this target is in clinical practice. Aim To assess the adequacy of blood pressure control in patients with type 2 diabetes attending a busy outpatient clinic. Methods One hundred and eight patients with type 2 diabetes were assessed for the presence of hypertension using a cut-off value of 130/85mmHg. Antihypertensive treatment and diabetic complications were evaluated. Results Hypertension was present in 67% of patients, in whom 90% were receiving anti-hypertensive treatment.. Forty-nine per cent of the treated patients achieved target blood pressure. Of the undertreated patients, 55% were on one antihypertensive agent, 30% were on two agents and 15% were on three or more agents. The corresponding figures for the adequately treated patients were 28%, 31% and 41%, respectively (p=0.03). Conclusion Adequate blood pressure control was underachieved in this patient group underlying the difficulty in treating blood pressure to target values in patients with type 2 diabetes in the setting of outpatient diabetes clinics. A more aggressive strategy, in particular the use of multiple antihypertensive agents should be adopted.