585

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rises of the rat isolate the lunction of ner- . . . ..--.

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d VD, this study.suggests that cled~onatc 1.1 in hn”. -._ _-._-_.. _~

of. 1988. JAutonom NehSyst 25:119.

586

AUTOSOMAL RECESSIVE INHERITANCE IN PSEUDO- HYPOPARATHYROIDISM TYPE In: A CASE REPORT. &,

University of Milan, Milnn, Italy. Known pedigrees of families with pseudohypoparathyroidism type

IP (PHP-la) have suggested X-linked dominant, autosomal dominant and, in only one report, autosomal recessive inheritance of the disease.We repon a case of a fumily in which a autosomal inheritance pattern was observed.

Two siblings of differen? sexes were referred to our attention with the classical feature of Albright hereditary osteodistrophy (AHO): the male was I8 years of age (Case A) and the female was I6 (Case B). Both otosented the classic AH0 DhenotvDe. with round face. short stature. obesity. osteodistrophy. brachy&faiy. brachydactily, soft tissue calcifications and exotropk Biochemical studies revealed decreased serum levels of total and Ionized cttlcium and of 1,25(OH),D3. slightly elevated values of serum phosphorus, normal magnesium and very elevated concentrations of PTH. Both urinary CAMP and phosphate did not increase after the PTH infusion test. Case B had hypothyroidism, whereas her brother showed only elevated levels of TSH, but normal concentmtion of free thyroid hormones. IQ was below normal in both siblings. They had normal karyogrums. Therapy with vitamin D restored the biochemical parameters. L-Thyroxine therapy was given to sibling B.

The parents did not show any of the characteristics of AHO; their heights were I75 cm (ftdther) and 168 cm (mother). They had normal serum values of calcium, phosphorus. and PTH, and they did not show metacarpal alterations on tadiologic examination.

The clinical feature, the biochemical alterations and the lack of response to the PTH infusion test lead to the diagnosis of PHP type la. The absence of somatic tmits of PHP-Ia in the parents excludes a dominant inheritance, while X-linked transmission has been excluded, &en the different sex of the siblings. We therefore conclude t!tat the possible form of genetic transmission in this family would appear to be a recessive uutosomal inheritance.

PROBLEMS IN THE LONG TERM THERAPEUTICAI MANAGEMENT. $F HY~OrPAR_~THYRO~IDISM II CH;;I)-I;;D. G eber. S. o a. M I Gua en. D. Pasolin

n. e . + Manenti and G. Chiumello, ScientiFc Institute H Sa Raffaele. Dept. of Pediatrics, University of Milan. Milan. Italv.

Short teti studies have shown the efficacy and iafeti of 1.2 dihydroxyvitamin DJ (1,25(OH)zDa) in the treatment c hypoparathyroidism (HP), but its long term effects are not we defined. We therefore prospectively studied 9 hormone-deficient H patients, followed for a minimum of 1.58 to a maximum of 10.9 years. Of the 9 patients, 5 had congenital HP, 3 multiple endocrin deficiencies and 1 had thalassemia major. Seven patients were treate with 1,25(OH)zDj at a dose range of 20-60 ng/Kgfday and 2 receive la OH Ds at a dose ran e of 40-50 q,n<

b f day. The age at rh

beginning of the vitamin therapy ranged ram I to 13.41 year Calcium lactate or carbonate was associated when needed to maintain daily Ca intake of 600-1200 mg. In 2 patients we used thiazid diuretics in an effort to reduce renal Ca excretion.

During therapy none of the patients had episodes of seizures ( revealed catamcts. but 4 presented sporadic latent tetany signs. W found ionized Ca always below the normal range, while total Ca (TC; was below normal in the 37.1 f 22.5 % of the determinations. We trie to keep the TCa values 2SD below the normal mean value to avoi hypercalciuria. but our effort was successful only in 4 patient Hypercalciuric episodes in fact occurred in 58.5 4 38.0 % of th determinations and the urinary Ca/Cteatinine ratio was above nomtal i the 43.1 4 36.8 % of the cases. Renal echography revealed moderate1 severe nephrocalcinosis in 4 patients. The bone mineral contet measured by single photon absorptiometry was normal in all th patients, but the one with thalassemia, during the follow-up period.

Although the long term therapy with calcitriol OI la hydron calciferol enabled us to control the hypocalcemia symptoms, satisfactory Ca balance was not achievable, mainly in the patients wil congenital HP. Thus, the efficacy of the therapy with vitamin : metabolites is extremely variable, depending upon individu; responsiveness.

587 BIOCHEMICAL MARKERS OF BONE FORMATION IN HYPOPITUITARY ADULTS. s, & &&y& && l&.&e m gtld ,& &ER~& Department of Metabolic Medicine, St. Mary’s Hospital Medical School. Paddineton. London. WZ IPG. UK.

The effect ofirowth hormone (GH) on bone is mediated by the local production of somatomedins such as insulin like growth factor 1 (IGF-1). which stimu!ate osteoblast collagen synthesis and bone formation. Data from other studies suggest that bone density may be reduced in hypopituitarism, but the effect of GiI replacement on adult bone is unknown at present. There is little information on biochemical markers of bone formation in the untreated state. We have therefore studied 15 hypopituitary men (mean age 46 years) and 18 women (mean age 42 years), who were treated with standard hormone replacement regimens, including sex hormone therapy where appropri- ate. Serum samples for IGF- 1, osteocalcin and procolla- gen type 1 carboxyterminal propeptide (PlCP) were col- lected between 1 I .30 hours and 12.30 hours. Serum calcx- urn. phosphate, alkaline phosphatase and whole molecule parathyroid hormone and bone densitometry using a LUNAR DEXA system were also measured. Serum IGF-I levels were lower than normal (mean + SD 215 + 7 lnglml normal; 91 + 48ng/mI hypopituitary pcO.001). Serum IGF-I values did not correlate significantly with serum PlCP levels and both serum PICP and osteocalcin levels wtre within the age and sex related reference ranges. Serum PlCP values showed a positive correlation with serum oste~dlcin values (r = 0.579, p cO.COl)

We conclude that serum IGF-1 values, which reflect GH deficiency, do not correlate with markers of bone forma- tion in hypopituitary patients at baseline. The response of these markers IO long term GH treatment is at present unknown.

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