Pseudohypoparathyroidism (PsH) is a genetic disease characterized by hypocalcemia, hyperphosphatemia, and metabolic unresponsiveness to parathyroid hormone (PTH). The administration of PTH elicits neither a significant rise in serum calcium (calcemic response) nor a decrease in the renal tubule reabsorption of phosphorus (phosphaturic response). The diminished phosphaturic response is due to an inability of PTH to generate cyclic AMP in renal tubule cells. We investigated the question of whether hypocalcemia and deficient calcemic response to PTH are due to a similar cyclic AMP defect in bone or to an acquired vitamin D deficiency. Four patients were studied. The active form of vitamin D (1,25-dihydroxycholecalciferol) was measured in 3 and was low. Treatment with vitamin D2 restored the serum calcium and the calcemic response to PTH to normal without changing the impaired renal response. Bone biopsy was performed in 2 patients and showed morphologic evidence of increased osteoclastic activity and osteomalacia. The data indicate that the hypocalcemia and bone disease in PsH are due to active vitamin D deficiency, possibly resulting from the genetic renal lesion.

Pentagastrin is a potent stimulator of thyrocalcitonin secretion from "C" cells. Since medulllary carcinoma of the thyroid gland (MCT) is a tumor composed of "C" cells, pentagastrin was used to screen a large kindred with multiple endocrine neoplasia type II (MCT, pheochromocytoma (s), and parathyroid hyperplasia). Four children with no thyroid abnormalities evident on physical examination, with negative thyroid scans, and with normal levels of plasma thyrocalcitonin both before and after calcium infusion, were found to have elevated peripheral levels of this hormone following pentagastrin injection. All four children were found to have very small foci of MCT, in both thyroid lobes at the time of total thyroidectomy. Pentagastrin stimulation used conjointly with selective catheterization of the inferior thyroid vein provided even greater diagnostic accuracy in detecting elevations in thyrocalcitonin secretion. This test has great diagnostic utility, especially in screening patients with multiple endocrine neoplasia type II.

The phenomenon of ketosis has interested investigators and clinicians for many years. With the recent rapid strides in the understanding of fat metabolism and the central role of acetyl-CoA in intermediary metabolism (1-5), this subject has taken on added interest. Although it has long been recognized that the liver is the chief site of origin of the ketone bodies, the basis for this has only recently been clarified. Apparently, most tissues are capable of forming acetoacetyl-CoA during the normal course of fatty acid catabolism or by condensation of two molecules of acetylCoA, but only the liver both possesses an enzyme, deacylase, which removes CoA from the molecule to release free acetoacetate, and at the same time lacks the acetoacetate activating enzyme which would result in acetoacetate's re-entering the metabolic cycle as acetoacetyl-CoA. Other tissues have some deacylase activity, but their acetoacetate activating enzyme system is so active that little or no free acetoacetate ever escapes from the cell (4). Ketonemia thus represents the balance between the rate of ketone production by the liver, utilization by extra hepatic tissues and excretion by the kidneys. Hepatic ketone production in turn is a function of the relative rates at which acetyl-CoA and acetoacetyl-CoA are formed, as from fat catabolism, and amino acids, and the rate at which acetyl-CoA can be disposed of by oxidation via the Krebs cycle or by reduction and syn-1

(22,23). A few studies of the qualitative nature of the urinary steroids in patients with this type of tumor seem to confirm such a conclusion (13,24). Accordingly, when the opportunity arose to study a patient bearing a testicular -tumor thought to be of this type, it seemed worthwhile to attempt to establish the exact nature of the steroids produced. The study presented here was therefore undertaken.This paper presents a description of the patient, histological observations on the tumor, the results of urinary steroid assays and the results of experiments in which slices of the tumor were incubated with C14-labeled steroid precursors. EXPERIMENTAL AND RESULTS