Galactorrhea-amenorrhea syndrome: follow-up of forty-five patients after pituitary tumor removal

Forty-five patients with galactorrhea-amenorrhea were followed during a period of 1 to 8 years (mean 3.1) after transsphenoidal prolactinoma removal. The ratios of patients who appear to be cured to the total numbers treated were 20 patients of 27 with grade I tumors; six of 10 with grade II; two of five with grade III; and none with grade IV tumors. Six patients with normal prolactin levels one week postoperatively had relapse later, as did three with normal prolactin levels 2 months postoperatively. A normal prolactin level 6 months postoperatively predicted ultimate cure. The 19 pregnancies that occurred in 15 patients, four with high prolactin levels, were uneventful. Prolactin rose normally with pregnancy and returned to prepregnancy level in all but one patient. Prolactin responses to stimulation tests were blunted for 6 months after successful tumor removal. By 1 year, responses to thyrotropin releasing hormone and metoclopramide tests were returning to normal, although responses to chlorpromazine and hypoglycemia remained blunted. The postoperative inhibition of normal lactotropes for 6 months is suggested. Ultimate cure cannot be determined before 6 months and conception should be deferred until then.     

Recovery of parathyroid hormone secretion after parathyroid adenomectomy

Using a sensitive two-site immunoradiometric assay which detects only intact human PTH-(1-84), we studied the kinetics of PTH secretion in 19 patients undergoing unilateral neck exploration and removal of a parathyroid adenoma. Preoperative serum PTH values averaged 116 ng/L (normal, 12-65 ng/L). In 8 patients in whom intraoperative sampling was performed, clearance of PTH-(1-84) was rapid, with virtual disappearance of PTH by 120 min after clamping the vascular pedicle to the adenoma. Analysis of the rate of disappearance of PTH-(1-84) indicated an exponential decay with a half-life of 21 min. Thirteen of 19 patients had serum PTH values less than 1 ng/L within 8 h after parathyroidectomy. Recovery of PTH secretion from the suppressed nonsurgically manipulated parathyroid tissue occurred during the nadir of postoperative hypocalcemia. Serum PTH was greater than 10 ng/L in 16 of 19 patients 30 h after removal of the PTH adenoma. Therefore, the functional recovery of atrophic parathyroid tissue is more rapid than that of other endocrine tissues studied to date.     

Reduction of a pancreatic tumor after total removal of an ACTH secreting pituitary tumor: differential diagnosis of Cushing's syndrome

Endocrinologic tests sometimes fail to distinguish adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma from ectopic ACTH-secreting tumor. The authors experienced a case of Cushing's disease associated with a pancreatic tumor. Venous sampling contributed to the final diagnosis of Cushing's disease in this complex case, while endocrinologic tests showed paradoxical results. A 54-year-old woman presented with Cushing's syndrome and pancreatic tumor. Magnetic resonance imaging (MRI) failed to reveal a pituitary tumor, but a gadolinium-enhanced tumor with cystic components was seen in the pancreatic tail. Results of conventional endocrinologic tests suggested ectopic ACTH syndrome, but venous sampling including cavernous sinus sampling indicated an ACTH-secreting pituitary adenoma. Transsphenoidal surgery revealed a pituitary microadenoma, and total removal of the tumor was achieved. Postoperative abdominal MRI revealed that the pancreatic tumor diminished gradually without treatment. Selective cavernous sinus sampling was useful for distinguishing ACTH-secreting pituitary adenoma from ectopic ACTH syndrome in this complex case. This was a rare case in which the pancreatic tumor diminished after total removal of the ACTH-secreting pituitary adenoma.     

The use of rapid parathyroid hormone assay in predicting postoperative hypocalcemia after total or completion thyroidectomy.

PURPOSE: To evaluate the rapid parathyroid hormone assay (rPTH) as a perioperative tool in predicting postoperative symptomatic hypocalcemia following thyroidectomy. METHODS: We conducted a prospective study of 69 patients undergoing total or completion thyroidectomy. Rapid PTH levels were obtained preoperatively, intraoperatively, and postoperatively upon arrival in the postanesthesia care unit (PACU). All patients were closely monitored postoperatively for the development of symptomatic or asymptomatic hypocalcemia. RESULTS: Of 60 patients (25%) undergoing thyroidectomy, 15 developed hypocalcemia, 7 (11.7%) were symptomatic, and 8 (13.3%) asymptomatic. An intraoperative rPTH level less than 12 pg/mL was 71% sensitive and 95% specific for predicting postoperative symptomatic hypocalcemia, whereas a PACU rPTH level less than 12 pg/mL was 100% sensitive and 92% specific. A greater than 75% decline in preoperative rPTH level when measured intraoperatively was 71% sensitive and 86% specific, whereas a greater than 75% decline in rPTH level in the PACU was 100% sensitive and 88% specific for predicting symptomatic hypocalcemia. CONCLUSIONS: The rPTH assay is a highly accurate and effective tool for predicting symptomatic hypocalcemia immediately after thyroidectomy. Routine utilization of this assay is recommended, because it will allow safe and timely discharge of normocalcemic patients and the early identification of patients requiring treatment of postthyroidectomy hypocalcemia.     

Subclinical Cushings disease with amelioration of metabolic comorbidities after removal of pituitary tumor

A 49-year-old woman with hypertension, obesity and impaired glucose tolerance (IGT) was admitted for evaluation of pituitary incidentaloma. Although she presented no Cushingoid feature, endocrine examination of hypothalamo-pituitary-adrenal (HPA) axis showed elevated basal plasma ACTH and cortisol levels, their lack of circadian rhythm, non-suppressibility to low-dose (1 mg) dexamethasone, and responsiveness to CRH, suggesting autonomous ACTH secretion from a pituitary tumor. She underwent transsphenoidal surgery, and was diagnosed as chromophobe adenoma with positive ACTH immunoreactivity. Postoperatively, her abnormal HPA axis was resolved, along with improvement of hypertension, obesity and IGT. Thus, her metabolic comorbidities are likely due to subclinical Cushings disease.     

Childbearing and the risk of parathyroid adenoma – a dominant cause for primary hyperparathyroidism

OBJECTIVES: To explore possible associations between the reproductive history amongst women and the risk of parathyroid adenoma (PA). DESIGN: Two nationwide Swedish registries. The Fertility Register included data on more than 3.4 million livebirths between 1943 and 1992 amongst Swedish females born 1925-72. The Cancer Register encompasses more than 1800 women with a diagnosis of PA 1960 until 1992. SETTING: All women resident in Sweden 1960-92. SUBJECTS: Cases were all 1800 women born 1925-72 reported to the Swedish Cancer Registry with a histopathological diagnosis of PA. Five controls were selected at random for each case by matching for the month and year of birth. Conditional logistic regression was used to estimate relative risks of PA. MAIN OUTCOMES: Parathyroid adenoma. RESULTS: High parity (four or more live births) was associated with an increased risk of PA. Amongst women with a diagnosis of PA before menopause (i.e. the age of 50 years) there was an increased risk of PA with younger age at first childbirth. Nulliparous women were at increased risk for PA before menopause, and at decreased risk after menopause. CONCLUSIONS: There is an association between childbearing and the risk of PA, which has not previously been demonstrated, but the underlying biological mechanisms remain to be determined.     

Documentation of parathyroid carcinoma fifteen years after resection of a parathyroid 'adenoma'

This report describes a 40-year-old man in whom the diagnosis of parathyroid carcinoma was made almost 15 years after resection of the primary lesion. The case emphasizes the importance of recognizing pre and intraoperative factors that differentiate between parathyroid adenoma and carcinoma and illustrates that surgical palliation is feasible in selected patients with parathyroid carcinoma.     

Elevated angiotensin II and vasopressin in primary hyperparathyroidism. Angiotensin II infusion studies before and after removal of the parathyroid adenoma

In order to evaluate the role of calcium metabolism in blood pressure regulation, 15 patients with primary hyperparathyroidism and 9 healthy control subjects were studied before and during angiotensin II infusion. The patients were re-investigated 2-5 months after removal of the parathyroid adenoma. Blood pressure, plasma levels of angiotensin II, aldosterone, arginine vasopressin, and atrial natriuretic peptide, and creatinine clearance were determined. Blood pressure and the blood pressure response to angiotensin II infusion were both the same before and after the operation. Angiotensin II and arginine vasopressin during basal conditions were significantly higher before than after the operation (angiotensin II: 17 (median) to 10 pmol/l, P less than 0.02; arginine vasopressin: 2.9 to 1.9 pmol/l, P less than 0.01), whereas aldosterone, atrial natriuretic peptide, and creatinine clearance were unchanged. During angiotensin II infusion, aldosterone, arginine vasopressin, and atrial natriuretic peptide increased to approximately the same levels before and after the operation. Blood pressure was not correlated to any of the hormones measured. Thus, patients with primary hyperparathyroidism have elevated plasma levels of angiotensin II and arginine vasopressin which may be compensatory phenomena counteracting volume depletion owing to a decreased renal concentrating ability induced by hypercalcemia, and owing to PTH-induced inhibition of renal sodium reabsorption.     

Somatic integration of an oncogene-harboring Sleeping Beauty transposon models liver tumor development in the mouse

The Sleeping Beauty (SB) transposon system can integrate foreign sequences of DNA in the genome of mouse somatic cells eliciting long-term expression in vivo. This technology holds great promise for human gene therapy as a nonviral technology to deliver therapeutic genes. SB also provides a means to study the effects of defined genetic elements, such as oncogenes, on somatic cells in mice. Here, we test the ability of the SB transposon system to facilitate somatic integration of a transposon containing an activated NRAS oncogene in mouse hepatocytes to elicit tumor formation. NRAS oncogene-driven tumors developed when such vectors were delivered to the livers of p19Arf-null or heterozygous mice. Delivery of the NRAS transposon cooperates with Arf loss to cause carcinomas of hepatocellular or biliary origin. These tumors allowed characterization of transposon integration and expression at the single-cell level, revealing robust NRAS expression and both transposase-mediated and random insertion of delivered vectors. Random integration and expression of the SB transposase plasmid was also observed in one instance. In addition, studies using effector loop mutants of activated NRAS provide evidence that mitogen-activated protein kinase activation alone cannot efficiently induce liver carcinomas. This system can be used to rapidly model tumors caused by defined genetic changes.     

The importance of the unsuppressed glands in the study of intact parathyroid hormone disappearance after parathyroid adenomectomy

BACKGROUND: In the usual techniques for intraoperative intact parathyroid hormone (iPTH) monitoring for primary hyperparathyroidism, the normal glands are implicitly considered suppressed. On the contrary, we believe, as do other researchers, that they are not totally suppressed. METHODS: For this reason, we considered the introduction of an infusion from the unsuppressed normal glands (UNG), described by an influx constant (IC (pg/ml per min)), into the formulation of a two-compartment model. For the blood compartment, we have: C(t)=A.exp(-at)+B.exp(-bt)+EV, where A+B+EV=iPTH concentration at zero time (clamping), EV (equilibrium value)=IC/k, 'a' and 'b' are reciprocals of the time constants of the two exponentials and k=rate constant of elimination from the blood. The experimental data were obtained using an IRMA standard method, collecting samples in 20 patients, during and following adenomectomy. RESULTS: In spite of the variability among the patients, all fits were very good, thus confirming the importance of the UNG contribution to the shaping of the disappearance curve. For this reason, the relationship between the constant infusion from the UNG and the basal iPTH level at the induction of anaesthesia (BV), was studied. CONCLUSIONS: The existence of a negative correlation, together with the determination of a regression curve (IC=6.5BV), not only confirmed our assumptions, but also revealed the theoretical possibility of a priori knowledge of the iPTH contribution from the UNG. Hence, there is a theoretical possibility of discriminating between this contribution and that of the remaining (if any) affected gland(s).