Subject(s)
Graves Disease/complications , Pseudohypoparathyroidism/complications , Aged , Autoimmunity , Biomarkers/blood , Calcium/blood , Cyclic AMP/urine , Diagnostic Techniques, Endocrine , Female , Humans , Hypocalcemia/etiology , Parathyroid Hormone/blood , Phosphorus/blood , Pseudohypoparathyroidism/classification , Pseudohypoparathyroidism/diagnosis , Pseudohypoparathyroidism/immunologySubject(s)
Adrenocorticotropic Hormone/physiology , Adenoma/metabolism , Adrenal Cortex/metabolism , Adrenal Cortex Neoplasms/metabolism , Adrenocorticotropic Hormone/deficiency , Animals , Arachidonic Acids/metabolism , Autoimmune Diseases/metabolism , Cholesterol/metabolism , Cyclic AMP/biosynthesis , Guinea Pigs , Humans , Pseudohypoparathyroidism/immunology , Pseudohypoparathyroidism/metabolism , RatsABSTRACT
We examined the effects of serum from a patient with pseudohypoparathyroidism type II and Sjögren's syndrome on renal function in rats. Infusion of 50-100 mg of the patient's immunoglobulin G (IgG) fraction inhibited the PTH-induced increase in urinary phosphate excretion, but had no effect on the PTH-induced increase in urinary cAMP excretion. Infusion of the IgG fraction obtained from the sera of control subjects did not affect PTH-induced increases in urinary excretion of either cAMP or phosphate. Binding of the patient's serum IgG fraction to the membrane of isolated rat renal cortical tubules was observed by immunofluorescent techniques. We conclude that the IgG fraction from the serum of this patient with pseudohypoparathyroidism type II and Sjögren's syndrome contains an autoantibody(ies) reacting with a component(s) of renal tubular plasma membranes and blocking PTH-induced phosphaturia.
Subject(s)
Autoantibodies/isolation & purification , Kidney Tubules/immunology , Parathyroid Hormone/antagonists & inhibitors , Phosphates/urine , Pseudohypoparathyroidism/immunology , Sjogren's Syndrome/immunology , Adult , Cell Membrane/immunology , Cyclic AMP/urine , Female , Humans , Kidney Cortex/immunology , Pseudohypoparathyroidism/metabolism , Sjogren's Syndrome/metabolismABSTRACT
Studies of the hormone-receptor interaction have introduced a new chapter in endocrine and metabolic disorders. Receptor (R) dysfunction in human diseases, due either to an alteration in the number or affinity of the R, or to antibodies against the R, is reviewed and classified in the first part of this paper. Disorders where hormone resistance has been implicated, but where R studies are still unavailable are also presented.
Subject(s)
Hormones/physiology , Receptors, Cell Surface/physiology , Acanthosis Nigricans/complications , Acanthosis Nigricans/physiopathology , Antibodies/analysis , Cell Nucleus/metabolism , Cytoplasm/metabolism , Diabetes Complications , Diabetes Insipidus/immunology , Diabetes Mellitus/physiopathology , Dwarfism/immunology , Graves Disease/immunology , Humans , Hypercholesterolemia/genetics , Hypercholesterolemia/physiopathology , Insulin/immunology , Insulin/physiology , Myasthenia Gravis/immunology , Obesity/physiopathology , Pseudohypoparathyroidism/immunology , Receptors, Cell Surface/immunology , Receptors, Cell Surface/metabolismABSTRACT
Because thyrotropin deficiency may occur in pseudohypoparathyroidism, we studied pituitary function in two families with this condition. Six of eight patients had impaired pituitary prolactin secretion after administration of thyrotropin-releasing hormone and chlorpromazine, with preservation of other anterior pituitary functions. Peak serum prolactin levels after thyrotropin-releasing hormone and chlorpromazine in the prolactin-deficient patients were significantly lower than normal. Administration of diethylstilbestrol for five days, which normally enhances prolactin responses to thyrotropin-releasing hormone, had no effect on prolactin secretion in these patients. Although antilactotroph antibodies were not demonstrable, hypothyroidism or decreased thyroid reserve in four and antithyroid and antiparietal-cell antibodies in several family members suggest that an associated autoimmune process may be responsible for the prolactin deficiency.
Subject(s)
Prolactin/deficiency , Pseudohypoparathyroidism/physiopathology , Adolescent , Adult , Aged , Autoantibodies/analysis , Autoimmune Diseases/physiopathology , Child , Child, Preschool , Chlorpromazine , Diethylstilbestrol/pharmacology , Female , Humans , Male , Middle Aged , Pituitary Function Tests , Prolactin/metabolism , Pseudohypoparathyroidism/diagnosis , Pseudohypoparathyroidism/immunology , Receptor, Insulin , Secretory Rate/drug effects , Thyroglobulin/immunology , Thyroid Function Tests , Thyrotropin-Releasing HormoneABSTRACT
Studies are presented in a patient with pseudohypoparathyroidism who showed a partial response to parathyroid extract. Resistance to the extract was observed after its short-term administration for the gourth time. Serum from the patient contained antibodies of the gamma G globulin class which bound 125I-labelled bovine parathyroid hormone. Prior incubation of parathyroid hormone with the serum prevented the activation in vitro of adenylate cyclase from pork renal cortex. The antibodies were directed primarily toward the C-terminal portion of the molecule. Thus, clinical resistance to parathyroid hormone is attributed to specific antibodies.
