Food-dependent androgen and cortisol secretion by a gastric inhibitory polypeptide-receptor expressive adrenocortical adenoma leading to hirsutism and subclinical Cushing's syndrome: in vivo and in vitro studies.

Aberrant gastric inhibitory polypeptide (GIP) receptor expression in bilaterally hyperplastic adrenals or unilateral adrenal adenomas is a rare form of adrenal hyperfunction. So far, only few cases have been described. In all these cases, cortisol was the predominant steroid released in a food-dependent manner, leading to the development of non-ACTH-dependent Cushing's syndrome. In the present study, we describe a novel case of a GIP receptor-expressive adrenocortical adenomatous nodule, detected incidentally by computed tomography scanning in a 41-yr-old lady with hirsutism but no clinical signs of Cushing's syndrome, on physical examination. Hormonal investigations in morning fasting samples showed slightly elevated androgen levels, low-normal baseline cortisol, normal suppression of cortisol after dexamethasone administration, and ACTH levels that were not suppressed and did stimulate after CRH administration. The elevated urinary free cortisol excretion, in conjunction with an atypical cortisol diurnal rhythm, raised the possibility of an aberrant stimulation of cortisol production by the adrenal tumor. Further studies demonstrated food-dependent secretion of cortisol, which was abolished by prior octreotide administration. Notably, substantial amounts of adrenal androgens were also secreted after food consumption. Removal of the tumor resulted in undetectable cortisol and androgen levels that did not respond to food consumption. Histological examination of the excised tumor revealed an adrenocortical adenomatous nodule originating from the inner zona reticularis, consisting mainly of compact cells. A steroidogenic secretory pattern, indicating the concomitant release of adrenal androgens and cortisol, was also observed in vitro from tumor cells cultured in the presence of GIP. The in vitro secretory response to GIP was higher for the adrenal androgen DHEA, compared with cortisol. The expression of the GIP receptor in tumor cells, but not in the adjacent normal adrenal, was demonstrated by RT-PCR), using specific oligonucleotide probes for this receptor. In summary, we describe a patient with a GIP-expressive cortisol and androgen oversecreting adrenocortical nodule with the unusual presentation of hirsutism and not the typical clinical signs of Cushing's syndrome. It is of note that food intake in this patient provoked a substantial increase in both adrenal androgen and cortisol levels that, together with the histological appearance of this nodule, was compatible with a zona reticularis-derived tumor. Thus, aberrant expression of the GIP receptor does not exclusively involve cells of a zona fasciculata phenotype, as previously reported, but may also occur in other types of differentiated adrenocortical cells.

Effect of 131I treatment on the calcitonin response to calcium infusion in hyperthyroid patients.

OBJECTIVE: The objective was to evaluate the effect of 131I treatment for hyperthyroidism on calcitonin secretion by thyroid C-cells. DESIGN: Determination of basal calcitonin levels and calcitonin secretory reserve before and after 131I administration. PATIENTS: Seventeen hyperthyroid patients (15 female, two male) were studied before, and 2 months after 131I treatment, and 12 of these patients were restudied 8 months after 131I treatment. MEASUREMENTS: Calcitonin response was assessed by measuring basal and post calcium infusion calcitonin levels. Basal TSH, T3, and T4 levels were also determined at each study. RESULTS: The rise of plasma calcium resulted in statistically significant increase of plasma calcitonin levels before 131I treatment (10.9 +/- 2.4 pmol/l), while this response was significantly diminished 2 and 8 months after treatment (2.6 +/- 0.7 and 1.6 +/- 0.3 pmol/l, respectively). No correlation was found between the calcitonin response and age or plasma TSH. CONCLUSION: Our results demonstrate that 131I treatment for hyperthyroidism may seriously damage thyroid C-cells and cause calcitonin deficiency.

The effect of cimetidine on parathyroid function and histopathology in primary hyperparathyroidism.

Recent evidence suggests that cimetidine given pre-operatively in primary hyperparathyroidism (1 degree HPT) might cause structural changes in parathyroid glands, while its suppressive effects on the disease are disputable. To determine these possible changes we studied 38 patients with 1 degree HPT who underwent parathyroidectomy. In 14 of these (group I) cimetidine was given pre-operatively (1000 mg orally daily for 4 weeks). The remaining 24 patients (group II) did not take any drug. Parathyroid function was estimated by nephrogenous cAMP (NcAMP) and serum immunoreactive parathyroid hormone (iPTH) measurements. Histological examination of the parathyroids was made by conventional techniques. In group I at the end of cimetidine treatment, the only change observed was a small but significant (p less than 0.05) decrease of plasma calcium (-0.77 mg/dl). Histologically, the glands of group I--compared with those of group II--showed the following findings: increased gland mass: mean increase 1050 mg (adenomas) and 700 mg (hyperplasias); central oedema in all the cases of group I only; increased (about 50 per cent) cellular size and intranuclear 'inclusions' in 10 out of 14 cases of group I only. It is concluded that treatment with cimetidine in 1 degree HPT is followed by histopathologic alterations leading to increased size of the diseased parathyroids.