We describe here a patient with primary hyperparathyroidism who had high serum intact PTH levels for over 16 months after parathyroidectomy without signs of recurrence or persistence of the disease. The patient was a 48-year-old female who appeared well nourished (body mass index, 23.7). She was received subtotal gastrectomy as treatment for a duodenal ulcer at 44 years and 5 months old and had reached menopaused at 46 years of age. Hypercalcemia and a high serum intact PTH level were pointed out three months before admission to our institute. A bone densitometric study revealed that the bone mass of the lumbar spine was extremely reduced (0.636g/cm₂, Z score, -2.17) preoperatively and had not increased 29.5 months after parathyroidal adenomectomy (0.656g/cm₂, Z score, -1.97).Hyperparathyroidism, menopause and gastrectomy may have together contributed to the reduced bone mass. The postoperative persistently increased PTH levels in our patient suggest that the remaining parathyroid glands could have been altered during hypercalcemia, causing an increase in the set-point of PTH secretion by serum calcium or a decrease in the renal responsiveness to PTH during the disease.

View full abstract

A 49 year-old Japanese woman had subjected enlargement of a cervical tumor, and also suffered two bone fractures in 2 years. The cervical tumor had enlarged further in the month prior toadmission, becoming warm and tender. Endocrinological examination revealed that the serum intact PTH concentration was remarkably high at 400 pg/mL despite the low serum calcium concentration, and that the serum vitamin Ds concentration was decreased. Bone roentgenograms revealed severe osteolytic changes compatible with osteitis fibrosa cystica and a pathologic fracture of the humerus.Under a diagnosis of primary hyperparathyroidism, parathyroidectomy was performed, followed by fixation surgery for the pathologic fracture. Histologically, the cervical tumor was a parathyroid chiefcell adenoma with massive necrosis, and the bone pathology by iliac bone biopsy revealed the existence of osteomalacia. She was treated with calcium, vitamins D and K2 and calcitonin after the surgery. This case is a rare condition manifesting hypocalcemia with catastrophic osteoporosis under the coexistence of spontaneous infarction of parathyroid adenoma with osteomalacia, suggesting that the clinical features of hyperparathyroidism are modified by both the autoparathyroidiectomy and the existence of osteomalacia due to vitamin D deficiency.

View full abstract

A mitochondrial DNA (mt DNA) point mutation at nucleotide pair (np) 3316 has been reported in relation to diabetes. We recently encountered a non-obese family with this type of mutation. The proband in the affected family, a 49-year-old woman who had been previously diagnosed as having an insulin-requiring non-insulin-dependent diabetes mellitus (NIDDM), was referred to our hospital for treatment of diabetic gangrene in her left foot. Her insulin secretory capacity was markedly reduced, but the insulin sensitivity evaluated by the euglycemic hyperinsulinemic clamp technique was normal.In addition, her serum lactate level was markedly increased after a 5 min ambulation, although her serum pyruvate and ketones remained within the normal range. Twenty-year-old twin sons had been treated with insulin since the age of 7, when both were diagnosed with insulin-dependent diabetes mellitus (IDDM). The proband's mother, a 68-year-old, was nondiabetic at this time. MtDNA analysis revealed a point mutation at np 3316 in all family members, which was homoplasmic for the mutation on a photograph of agarose gel electrophoresis containing ethidium bromide under ultraviolet light.This mutation seemed to be maternally transmitted in the family, and the onset of diabetes was occurring earlier and the insulin secretory capacity was declining from generation to generation, so that these findings suggest that the point mutation at np 3316 is associated with various phenotypes of diabetes.

View full abstract

There has been accumulating evidence that pituitary adenomas which cause Cushing's disease are located not only in sella turcica but also in various extrasellar and intracranial regions. We describe a case of Cushing's disease caused by a supra- and extrasellar ACTH-producing microadenoma, which originated in the anterior pituitary and extended upward without connecting to the stalk. The pituitary microadenoma was identified and removed by transsphenoidal microsurgery. After the surgery the patient experienced complete remission. This type of pituitary microadenoma is considered to be rare, but in order to accomplish successful surgical treatment, it is necessary to consider that pituitary adenomas which cause Cushing's disease may be located in such an unusual position.

View full abstract

Familial hyperparathyroidism (FHPT) is a hereditary disease where hyperparathyroidism (HPT) is transmitted in an autosomal dominant fashion. FHPT consists of a variety of diseases such as multiple endocrine neoplasia type1 (MEN 1) and type2 (MEN 2), familial isolated hyperparathyroidism (FIHPT) with single adenoma and with multiple adenomas (or hyperplasia), and FHPT with jaw-tumor (FHPT-JT). Isolation of the genes responsible for MEN 1, and 2, i.e. MEN1 and RET, respectively, makes it possible to examine the relations among disorders constituting FHPT. We studied germ-line mutations in these 2 genes in a family of FHPT with single parathyroid adenoma. The disorder in this family was proved to be an entity different from MEN 1 because no germ-line mutations in MEN1 gene were found in the affected members. The loss of heterozygosity (LOH) at MEN1 gene and PYGM were not found in the abnormal parathyroid in this family, supporting the above conclusion. No mutations in exons 10, and 11 of RET proto-oncogene was found in germ-line DNA of the affected member of the family, suggesting no relation to MEN 2A. Linkage study excluded the possibility of FHPT-JT syndrome. PRAD1 was not overexpressed in the parathyroid tumors in this family. The relation of this disorder to FIHPT with multiple enlarged parathyroid glands remains to be clarified. A search for the gene (s) predisposing to FIHPT is needed.

View full abstract

The inhibitory effect of β₃-adrenoceptor agonists on the ob gene in brown adipose tissue (BAT) and white adipose tissue (WAT) is now well documented both in vivo in lean animals and in vitro, but the reported effects of β₃-adrenoceptor agonists on ob gene expression in obese animals remain controversial. We investigated whether ob gene expression in BAT and WAT is reduced by acute and chronic administrations of a β₃-adrenoceptor agonist, CL316, 243 (CL). The ob gene mRNA levels in BAT, perimetric and inguinal WAT of obese Yellow KK mice were about 4-fold higher than those of lean controls. Acute exposure (6 h) to CL decreased ob gene mRNA levels in three fat depots in both animals. Chronic exposure (10 days) to CL also decreased ob gene mRNA levels in BAT, perimetric, and inguinal WAT in both animals. We concluded that acute and chronic regulation by a β₃-adrenoceptor agonist suppressed ob gene expression in obese Yellow KK mice and lean cotrols.

View full abstract

We identified a novel nonsense mutation (R29X) of the MEN1 gene in a familial multiple endocrine neoplasia type 1 (MEN1) patient. Molecular analysis of the MEN1 gene was performed in the family members by a restriction digestion method. The same mutation pattern was seen in both theb proband's younger brother and cousin diagnosed as MEN1, and was also observed in the son of the cousin who showed signs of normal levels of serum PTH associated with mild hypercalcemia and hypophosphatemia. These findings suggest that mutation analysis of the MEN1 gene is very useful in identifying the subclinical state of MEN1 as well as clinical MEN1.

View full abstract

To evaluate the role of N-linked oligosaccharides in the molecular action of rat placental lactogen (PL), recombinant PL-Im (recPL-Im) and three recPL-Im mutants were produced in COS-7 cells. The mutants, carrying Gin substitutions of Asn at putative N-glycosylation sites, were generated via site-directed mutagenesis, i.e. two single mutants (N79Q, N128Q) and one double mutant (N79Q/N128Q). Western blot analysis revealed that wild type recPL-Im had a molecular mass of 34 kDa, which was reduced to 29 kDa by tunicamycin present during expression. N79Q and N128Q had a lower molecular mass than the wild type, and a further decrease was observed for N79Q/N128Q. PL-Im was therefore N-glycosylated at both Asn⁷⁹ and Asn¹²⁸. Treatment of the wild type with neuraminidase caused a reduction in molecular mass, indicating that the N-linked oligosaccharides contained N-acetylneuraminic acids. In the Nb2 cell bioassay for lactogenic hormones, recPL-Im and its mutants all had growth-promoting activity but there was a decline in the growth-stimulating potency following decreases in N-glycosylation, i.e. the order of relative potencies was the wild type>N128Q> N79Q>N79Q/N128Q, suggesting that the N-linked oligosaccharides are important in the mitogenic action of the PL-Im. Wild type and all mutants had rat PRL receptor (PRL-R)-binding activity in radioreceptor assays and stimulated JAK2 phosphorylation in Nb2 cells. Interestingly however, the binding activity to PRL-R and phosphorylation of JAK2 was similar in the wild type and mutants, and these results are not in accord with the biological activity. In conclusion, the study suggested that PL-Im has two N-linked oligosaccharides which are involved in its biological activity. The ability of PL-Im to bind PRL-R and activate JAK2 appears to be independent of the N-glycosylation.

View full abstract

Osteomalacia is a metabolic bone disease caused by deficiency of vitamin D or its active metabolites. Because poor sunlight exposure is one of the most common causes of osteomalacia, the disease seems to be rare in countries with adequate sunlight We report nine Turkish female patients with osteomalacia with ages between 21 and 50 years. Osteomalacia was diagnosed on the basis of a history of bone aches or pains, muscle weakness, low or low normal serum calcium and urinary calcium, decreased concentrations of serum inorganic phosphorus and 25-hydroxyvitamin D and increased serum intact PTH and alkaline phosphatase levels. Radiographically, pseudo-fractures were present in seven of the patients. The patients' symptoms and signs were relieved with the treatment with vitamin D analogues and calcium. Their hypovitaminosis D are suggested to be caused by excessive clothing in the outdoors due to sociocultural and religious reasons. Excessive clothing may be a risk factor for osteomalacia in young to middle-aged and otherwise healthy women even in countries with adequate sunlight.

View full abstract

A prospective study was performed to investigate postpartum changes in human bone metabolism and the effects of lactation on them. The subjects consisted of two groups: 13 women who stopped breast-feeding within 3 months postpartum (short-term group) and 14 women who continued breast-feeding for more than 6 months postpartum (long-term group). Serum carboxyl-terminal propeptide of type I procollagen (PICP), carboxyl terminal cross-linked telopeptide of type I collagen (ICTP), and bone gla protein (BGP) were measured prepartum, and at 5 days, 1 month, 3 months and 9 months postpartum. Lumbar BMD was measured at 3-7 days, 3 months and 9 months postpartum. Between prepartum and 3 months postpartum, the values and variations in the markers were essentially the same in both groups. PICP was maintained at a constant and significantly higher level than the control value. In contrast, ICTP had increased markedly at 5 days postpartum, gradually decreasing thereafter. BGP was low prepartum and gradually increased. At 9 months postpartum, PICP and ICTP decreased to the control values in the short-term group. The postpartum time course of lumbar BMD showed a significant decrease in both groups at 3 months postpartum. Recovery to the puerperal level was seen at 9 months postpartum in the short-term group but not in the long-term group. In conclusion, bone resorption is stimulated by parturition as well as lactation resulting in postpartum loss of lumbar BMD.

View full abstract

A 43-year-old woman was admitted to our hospital for further treatment of acromegaly with high plasma GH and IGF-I levels after transsphenoidal adenomectomy and subsequent treatment with bromocriptine.Physical examination and magnetic resonance imaging (MRI) showed anactive acromegalic appearance with residual pituitary macroadenoma.Laboratory findingsrevealed an increase in basal levels of plasma GH (21.3 μg/L) and plasma IGF-I (470 ng/ml). Plasma GH levels were suppressed from 21.3 μg/L to 9.9 μg/L following oral administration of 75 glucose and did not respond to either TRH or LHRH injection. When plasma GH levels were measured after repeated blood sampling every 20 min for 24 h and sleep stages were analyzed, there were three GH peaks during the night which corresponded to the slow-wave sleep. Mean plasma GH levels which corresponded to the slow-wave sleep stages were much greater than those of other sleep stages during the night. After the patient was treated with intermittent sc injections of octreotide (40 μg/every 2 h, 480 μg/day) in combination with oral administration of bromocriptine (15 mg/day, t.i.d.), episodic GH release was somewhat suppressed but plasma GH levels were slightly increased, corresponding to the slow-wave sleep stage during the night. Mean plasma GH levels were much higher during the sleeping period than the waking period for 24 h before and after the treatment. These findings suggest that GH secretion is correlated to the slow-wave sleep in this particular patient with pituitary GH producing adenoma.

View full abstract

We encountered a pregnant woman with transient diabetes insipidus which developed during the third trimester. A hypertonic saline infusion study did not concentrate the osmolality of urine. Her laboratory data showed hypokalemia, hyperreninemia, an increased concentration of plasma aldosterone and an increased urinary excretion rate of prostaglandin E2, which resembled hyperprostaglandin E-syndrome. T1-weighted magnetic resonance imaging of the posterior pituitary gland revealed decreased intensity. Polyuria reached 4-6 L daily, and urine osmolality remained dilute despite a lapse of four days since treatment with intranasal 1-desamino-8-D-arginine vasopressin (dDAVP: 10-25μg every 12 h). The patient was conservatively managed without medical treatment, then delivered in the 38th week of pregnancy without complication. The osmolality of the patient's urine was higher than that of the plasma when tested 3 days postpartum. The abnormality of magnetic resonance imaging of the posterior pituitary gland disappeared at 6 months after delivery. We consider that subclinical nephrogenic diabetes insipidus in our patient was exacerbated during pregnancy.

View full abstract

We report a 61-year old male patient with panhypopituitarism complicated with asymptomatic primary biliary cirrhosis (PBC). Tl-weighted magnetic resonance imaging demonstrated high intensity of the anterior pituitary gland. There was no mass lesion or enlargement of the pituitary gland or the stalk. Immunoblot analysis of the patient's sera with rat pituitary antigens revealed a band with a molecular size of 22 kD. Anti-M2 mitochondrial antibody has been consistently positive for five years. Liver biopsy revealed portal hepatitis with periportal infiltration of the inflammatory cells. This is the first case report of autoimmune hypophysitis complicated with asymptomatic PBC.

View full abstract