Encapsulated medullary carcinoma of the thyroid. A morphologic study including immunocytochemistry, electron microscopy, flow cytometry, and in situ hybridization.

An unusual encapsulated medullary carcinoma of the thyroid is reported. Immunocytochemistry and electron microscopy did not prove conclusively the cytogenesis of the tumor; however, in situ hybridization, by demonstrating the presence of calcitonin mRNA, revealed that the tumor is of C-cell derivation. Because these tumors have an unpredictable biologic behavior, it seems more appropriate to designate them as encapsulated medullary carcinoma than as C-cell adenoma. Immunocytochemistry for calcitonin and carcinoembryonic antigen as well as flow cytometry for DNA ploidy may be valuable techniques to assess prognosis of these tumors.

Cushing's syndrome due to unilateral nodular adrenal hyperplasia: a new pathophysiological entity?

A case is presented of a 43-year-old Caucasian female with Cushing's syndrome, malignant hypertension and renal insufficiency. Plasma cortisol values were elevated (19.5 microgram/100 ml at 0800 h and 18.5 microgram/100 ml at 2200 h) with loss of diurnal variation and failure of suppression with low and high dose dexamethasone. 17-ketogenic steroid excretion remained unchanged after metyrapone administration. Adrenal vein plasma cortisol values showed prominent left-sided gradient. Gross, histologic and electron-microscopic examination of the left adrenal gland revealed changes of nodular adrenal hyperplasia. The presence of a suppressed right adrenal gland was confirmed post-operatively by a five day ACTH infusion. This case may represent a previously unreported variant of Cushing's syndrome due to unilateral nodular adrenal hyperplasia.

The thyrotoxicosis of hydatidiform mole.

In 14 women with hydatidiform mole, 9 were hyperthyroid. Serum thyroxine (T4) levels varied between 18 and 34 mug/100 ml, and serum triiodothyronine (T3) levels between 300 and 800 ng/100 ml in the hyperthyroid patients. Bioassayable thyroid-stimulating hormone (molar TSH) was found in high concentrations in the serum of 13 patients in whom preoperative serum was available. There was a close correlation between the serum levels of human chorionic gonadotrophin, molar TSH, and T3. Intravenous sodium iodide caused a fall in serum T3 and, to a lesser extent, in T4 in hyperthyroid patients but not in a euthyroid patient. Removal of molar tissue caused a dramatic fall in the serum levels of T3, T4, molar TSH, and human chorionic gonadotrophin. The close correlation between the serum concentrations of molar TSH and human chorionic gonadotrophin lend support to the suggestion that the human chorionic gonadotrophin molecule itself, when present in large amounts, stimulates thyroid function significantly.

Pituitary melanocorticotrophinoma with amyloid deposition.

The light and electron microscopic features of a pituitary adenoma composed of adrenocorticotrophic hormone (ACTH) and melanocyte stimulating hormone (MSH) cells with perivascular amyloid deposition is reported. Histochemical and fine structural data indicate that this material is APUDamyloid and is present in the extra-cellular perivascular spaces. It is suggested that the differences in fine structure and of distribution of the amyloid in pituitary adenomas is dependent upon the cell of origin.

The thyrotropin in hydatidiform moles is human chorionic gonadotropin.

Thyrotropic activity (TSH), measured by the McKenzie mouse bioassay, has been correlated with human chorionic gonadotropin (hCG) activity, measured by radioimmunoassay, in serum and tissue samples from 11 patients with hydatidiform mole and in partially and highly purified preparations of urinary hCG. Serum samples, taken at various times before and after removal of the moles, gave a ratio of 0.42 plus or minus 0.24 muU TSH/U hCG (mean plus or minus SD) (N)=43). In all cases where hCG activity fell below 150-175 U/ml (n=49), thyroid stimulating activity was undetectable (smaller than 40 muU/ml). We extracted lyophylized molar tissue by a modification of the Bates alcohol-saline method and purified the resultant extract by a combination of gel chromatography, affinity chromatography using Concanavalin A coupled to Sepharose, and isoelectrofocusing. Following extraction, an approximately 20-fold purification was achieved without significant alteration of the ratio of the two activities. Using results from all phases of purification the ratio of muU TSH/U hCG was 0.51 plus or minus 0.35(n = 23). Both activities were in the same position on disc gel electrophoresis. Activity ratios were less constant when partially purified preparations of urinary hCG were assayed for both thyrotropic and hCG activities. The presence of an hCG immunoreactive species, presumably hCG-beta subunit, which contains no thyrotropic activity but has an approximately 10-fold greater activity on a weight basis than intact hCG, may be a partial explanation for this observation. Isoelectrofocusing of a urinary hCG preparation showed that all hCG immunoreactive species with pl's between 3. 5 and 5.0 contained thyrotropic activity in proportion to their hCG content. Seven highly purified hCG preparations had thyrotropic activity with a ratio of 0.48 plus or minus 0.18 muU TSH/U hCG. These results indicate that hCG has intrinsic thyrotropic activity. On a molecular basis it is calculated that hCG contains approximately 1/4000 the thyrotropic activity of human pituitary TSH. In conditions of grossly elevated serum hCG levels, such as hydatidiform mole, this thyrotropic activity can be sufficient to produce hyperthyroidism.

Apathetic thyrotoxicosis.

Apathetic thyrotoxicosis is an atypical though not rare manifestation of hyperthyroidism. The cardinal features are apathy and depression, as opposed to hyperkinesis and mental alertness in the usual thyrotoxic patient, and are unassociated with the usual signs and symptoms of hyperthyroidism, making the diagnosis difficult. We report three cases of apathetic thyrotoxicosis seen during one year.