ABSTRACT
Patients with pseudohypoparathyroidism type Ib (PHP-Ib) present hypocalcemia and hyperphosphatemia, as a consequence of a resistance to PTH action, through its G-protein-coupled receptor, in the renal tubules. This resistance results from tissue-specific silencing of the G-protein alpha-subunit (G(s)α), due to imprinting disruption of its encoding locus--GNAS. In familial PHP-Ib, maternally inherited deletions at the STX16 gene are associated to a regional GNAS methylation defect. In sporadic PHP-Ib, broad methylation changes at GNAS arise from unknown genetic causes. In this study, we describe the clinical presentation of PHP-Ib in four Portuguese patients (two of whom were siblings), and provide further insight for the management of patients with this disease. The diagnosis of PHP-Ib was made after detection of GNAS imprinting defects in each of the cases. In the siblings, a regional GNAS methylation change resulted from a known 3.0 kb STX16 deletion. In the other two patients, the broad methylation defects at GNAS, which were absent in their relatives, resulted from genetic alterations that remain to be identified. We report the first clinical and genetic study of Portuguese patients with PHP-Ib. The genetic identification of a hereditary form of this rare disease allowed an early diagnosis, and may prevent hypocalcemia-related complications.
Subject(s)
GTP-Binding Protein alpha Subunits, Gs/genetics , Pseudohypoparathyroidism/diagnosis , Adult , Child , Chromogranins , Female , Humans , Portugal , Pseudohypoparathyroidism/genetics , Syntaxin 16/genetics , Young AdultSubject(s)
Endocrine System Diseases/complications , Endocrine System Diseases/psychology , Mental Disorders/etiology , Humans , Mental Disorders/epidemiology , Mental Disorders/physiopathology , Pituitary Gland/pathology , Pituitary Gland/physiology , Prognosis , Quality of Life , Stress, Psychological , Treatment OutcomeABSTRACT
Non-puerperal lactation and/or hyperprolactinemia in humans have been related to psychological variables in a variety of ways: (1) Non-puerperal nursing; (2) Pseudopregnancy; (3) Rapid weight gain; (4) Psychogenic galactorrhea; (5) Acute prolactin responses to psychological stress; (6) High prolactin levels in persons who cope passively in real life stress situations; (7) Paternal deprivation in women with pathological hyperprolactinemia; (8) Clinical onset of prolactinomas following life-events. Publications on the above subjects are scattered in the literature as curiosities, anecdotal case-reports or unexplained associations, as there is no theoretical frame of reference to accommodate them. We propose that prolactin is a component of a biological, "maternal", subroutine, adaptive to the care of the young, which promotes accumulation of fat for the extraordinary expenses of pregnancy and lactation, the production of milk and maternal behavior. In an attempt to characterize the stimuli responsible for the activation of the maternal subroutine in the absence of pregnancy we studied the hormonal profiles of female volunteers during three types of sessions under hypnosis: (1) Relaxation-only, control sessions; (2) Sessions in which a fantasy of "nursing" was induced; (3) Sessions of evocations of memories. Prolactin surges were related to the evocation, with rage, of humiliating experiences, but not with the fantasy of nursing. Cortisol surges were related to surprise and shock and were negatively associated with prolactin. In conclusion--Prolactin and cortisol are measurable markers of two different, and alternative, coping strategies to "psychological stress".
Subject(s)
Adaptation, Physiological/physiology , Prolactin/physiology , Stress, Psychological/physiopathology , Environment , HumansABSTRACT
Small tumors producing adrenocorticophic hormone (ACTH) ectopically may be very difficult to locate. We describe a 57-year-old woman who presented with ectopic Cushing's syndrome as diagnosed by bilateral inferior petrosal sinus catheterization with corticotrophin-releasing hormone (CRH) test. Thoracic pentetreotide (a somatostatin analogue) revealed a small "hot spot" in the base of the left lung. This "hot spot" was constant throughout the procedure. A second thoracic CT scan with 3-mm cuts showed a small image in the area under suspicion, similar to vascular images found elsewhere in both lungs. At surgery, an 8-mm tumor was found and excised. Pathological examination revealed a carcinoid tumor immunoreactive for ACTH, beta-endorphin, bombesin, serotonin, and the α-subunit. One month after surgery, the patient was clinically well and had normal adrenal function. An111ln-pentetreotide scintiscan clearly identified a small ACTH-producing neuroendocrine tumor of the lung undetectable by plain chest radiography or CT scan.
