Role of the oral calcium-loading test with measurement of intact parathyroid hormone in the diagnosis of symptomatic subtle primary hyperparathyroidism.

BACKGROUND: This study was designed to assess the diagnostic value of the oral calcium tolerance test with measurement of intact parathyroid hormone by the immunoradiometric assay (IRMA PTH) in the diagnosis of primary hyperparathyroidism in patients with symptoms who have minimal, intermittent, or no elevation of the levels of total calcium and/or intact PTH. METHODS: After baseline levels of IRMA PTH and total calcium were measured, an oral calcium load of 1000 mg elemental calcium was administered to 10 patients with hyperparathyroidism and 18 normal control subjects. Total calcium and IRMA PTH levels were measured at 30, 60, and 120 minutes after the oral calcium load was administered. RESULTS: The mean suppression of the baseline level of IRMA PTH in the patients with hyperparathyroidism was 83.7% +/- 6.5% (mean +/- 1 SEM), but the levels of the normal control subjects fell significantly (p < 0.05) lower to 58.8% +/- 3.7% (mean +/- 1 SEM). CONCLUSIONS: This study suggests that the oral calcium tolerance test may be a valuable adjunct in confirming the diagnosis of primary hyperparathyroidism in patients with symptoms who have minimal, intermittent, or no elevation of the levels of total calcium and/or IRMA PTH:

Management of Cushing's syndrome secondary to adrenal adenoma during pregnancy.

This report discusses our experience with two patients who had unilateral adrenalectomy during pregnancy as treatment for Cushing's syndrome secondary to an adrenal adenoma. Previously only five patients with this clinical problem who underwent unilateral adrenalectomy during pregnancy had been reported. We have reviewed the world literature on Cushing's syndrome in pregnancy secondary to an adrenal adenoma. A total of 19 patients who had unilateral adrenalectomy for this problem after the completion of pregnancy were identified. The review of world literature and the two patients who are the subject of this report were the basis of our analysis of fetal death, neonatal complications, and maternal complications in seven pregnancies during which unilateral adrenalectomy was performed (group 1) compared to the 19 pregnancies that were associated with unilateral adrenalectomy at the completion of pregnancy (group 2). Of the seven pregnancies in group 1, one fetal death and no neonatal complications occurred, but fetal death and neonatal complications occurred in 12 of the 19 pregnancies in group 2. Four of the seven mothers in group 1 had complications; 16 of the 19 mothers in group 2 had complications. This study suggests that adrenalectomy during pregnancy should be considered as a therapeutic option in the management of Cushing's syndrome secondary to an adrenal cortical adenoma.

Ontogeny of thyrotropin-releasing hormone and histidyl proline diketopiperazine in the rat central nervous system and pancreas.

The ontogeny of TRH and of a proposed TRH metabolite, histidyl proline diketopiperazine (His-Pro DKP), was determined in the rat central nervous system and pancreas as a means of studying the interrelationship of these peptides. Various regions of the rat brain, spinal cord, and pancreas were dissected from animals ranging in age from prenatal day 17 to adult. The tissues were extracted for TRH and His-Pro DKP, and tissue levels of the two peptides were measured by specific RIAs. We found increasing TRH levels in the hypothalamus, spinal cord, and multiple extrahypothalamic brain regions in the developing rat [e.g. from 21 +/- 3 (+/- SE) pg/hypothalamus on prenatal day 17 to 2606 +/- 296 pg/hypothalamus in the adult]. In the rat pancreas, however, TRH levels initially increased from 354 +/- 37 pg/pancreas on prenatal day 21 to 749 +/- 68 pg/pancreas on postnatal day 7, but from day 7 to adulthood, the TRH content fell dramatically, being undetectable in the adult rat pancreas. The His-Pro DKP content increased in nearly all tissues studied, with peak values occurring on postnatal days 10 and 28 and in the adult. There was little apparent correlation, however, between the anatomical distribution and ontogeny of TRH compared with those of His-Pro DKP. We conclude that His-Pro DKP and TRH have widespread distributions involving the hypothalamus, extrahypothalamic brain, spinal cord, and pancreas in the developing rat. TRH and His-Pro DKP, however, have differing patterns of ontogeny in the rat, suggesting that His-Pro DKP may be derived from sources other than just TRH.

Use of a rapid, sensitive immunoradiometric assay for thyrotropin to distinguish normal from hyperthyroid subjects.

Using a new three-site immunoradiometric assay for thyrotropin (TSH), we measured concentration of this hormone in the serum of 47 patients with hyperthyroidism and 46 controls. The mean and range of serum TSH concentration was significantly lower in thyrotoxic than in control subjects, and it was possible to correctly identify 96% of thyrotoxic patients on the basis of a serum TSH concentration less than 0.5 milli-int. unit/L. We conclude that such measurement is highly sensitive for distinguishing hyperthyroid from normal subjects, and that the lower limit of normal for TSH in serum is about 0.5 milli-int. unit/L.

Von Willebrand factor (VIII R:Ag), fibronectin, and insulin-like growth factors I and II in diabetic retinopathy and nephropathy.

We have measured plasma von Willebrand factor (VWF) as the factor VIII-related antigen, plasma fibronectin, and two of the serum somatomedins, insulin-like growth factor I (IGF I) and IGF II, in 51 diabetic patients and 25 nondiabetic control subjects. VWF was significantly higher in the diabetic group than in the controls (173 +/- 9% SEM versus 101 +/- 9%, P less than 0.001), as has been reported by others. However, within the diabetic group there was no significant difference in VWF between those patients without retinopathy, those with background or proliferative retinopathy, or those with macular edema. There was also no difference in VWF between the diabetic subjects with and those without proteinuria. These results rule against a previously advanced hypothesis that the increase in VWF in patients with diabetes is secondary to microangiopathy. No significant difference was observed in fibronectin, IGF I, or IGF II between the diabetic and control groups, between the diabetic group without retinopathy and the retinopathic subgroups, and between the diabetic subjects with and without proteinuria. In the diabetic patients, there was no correlation between diabetic control as assessed by glycosylated hemoglobin and glycosylated serum protein, and the plasma levels of VWF, fibronectin, IGF I, or IGF II. The results of this study strongly suggest that neither plasma VWF, fibronectin, IGF I, nor IGF II plays an important primary role in the pathogenesis of diabetic microvascular disease, although one or more of these factors might play a permissive role.

Investigation of hypothalamic-pituitary disease.

It can be readily appreciated from the preceding discussion that many endocrine and non-endocrine tests are available for the evaluation of patients with suspected hypothalamic-pituitary disease. The endocrine evaluation of these subjects should be tailored according to the type and extent of pathology suspected (see Tables 2 and 3). For patients with pituitary adenomas and clinical features of hyperpituitarism, such as hyperprolactinaemia, Cushing's disease or acromegaly, the initial tests should be directed at the hormone whose excess is suspected. For example, a glucose suppression test for acromegaly or dexamethasone suppression test for Cushing's disease should be performed early in the evaluation. The possibility of deficiencies of the other pituitary hormones should then be addressed in patients with secretory tumours, but initially in those with apparent non-functioning adenomas. In patients with large macroadenomas pituitary hormone deficiencies are almost invariable with GH and FSH/LH being the most commonly affected, followed by TSH and ACTH in that order (Snyder et al, 1979a; Valenta et al, 1982). Basal thyroid function tests, serum oestradiol or testosterone, and basal gonodotrophins should be routinely obtained in patients with macroadenomas. Additionally, the integrity of the pituitary-adrenal axis should be determined and an overnight water deprivation test for assessment of neurohypophyseal function is also recommended. GH stimulation testing is valuable as a test of pituitary function in patients with suspected pituitary tumours since GH reserve is lost very early in the development of hypopituitarism. Evaluation of the pituitary-thyroid axis with TRH or the pituitary gonadal axis with LHRH generally provides limited additional information of diagnostic value in individual patients with macroadenomas. However, the 'paradoxical' responses to TRH and LHRH may be useful as a biological marker following therapy in patients with GH- or ACTH-secreting tumours. In patients with microadenomas, pituitary hormone deficiencies are uncommon (Valenta et al, 1982). Despite this observation, it may be beneficial to determine basal thyroid levels, gonadotrophin levels, serum testosterone or oestradiol levels, and the response to an overnight metyrapone test in such patients to provide a baseline for future care.(ABSTRACT TRUNCATED AT 400 WORDS)

Frequent falsely negative renal vein renin tests in unilateral renal parenchymal disease.

A retrospective analysis of 12 hypertensive patients with unilateral renal parenchymal disease was done to evaluate the roles of renal vein renin testing and an operation. The patients were considered to have renal parenchymal disease on the basis of radiographic and/or pathologic findings. Only 2 patients had positive renal vein renin studies. Both of these patients were improved after unilateral nephrectomy but 1 had subsequent progression of disease and renal failure. Of the 10 patients with negative studies 5 had unilateral nephrectomy: 4 of them, nevertheless, experienced substantial improvement in the hypertension. It is concluded that hypertensive patients with unilateral renal parenchymal disease often can benefit from an operation and that renal vein renin testing in such patients can be misleading.