Hyperprolactinemia and galactorrhea: spontaneous versus iatrogenic hypothyroidism.

Although hyperprolactinemia and galactorrhea occur in primary hypothyroidism, factors influencing their presence are not well established. To further define these factors, the duration of illness and serum levels of PRL and TSH were investigated in a group of 50 patients with spontaneous (27 females and 7 males) and iatrogenic (16 females) primary hypothyroidism. To test the hypothesis of reduced hypothalamic dopamine content in over long-standing primary hypothyroidism, the percent increase in serum PRL after the administration of metoclopramide, a dopamine blocker (2.5 mg, iv bolus), was studied in 13 women with spontaneous primary hypothyroidism and compared with that in 10 euthyroid women. While 88.2% of the patients with spontaneous primary hypothyroidism were hyperprolactinemia, only 31% of those with iatrogenic disease had elevated PRL levels. Women with spontaneous primary hypothyroidism had a longer duration of illness (72 +/- 12 vs. 6.7 +/- 1.8 months; P less than 0.001) and higher serum TSH (189 +/- 32 vs. 68 +/- 14 microunits/ml; P less than 0.01) and PRL levels (49.8 +/- 5.6 vs. 20.9 +/- 0.8 ng/ml; P less than 0.001) than women with iatrogenic hypothyroidism. A linear correlation existed between PRL and duration of illness (r = 0.53; P less than 0.001), while a logarithmic correlation was found between PRL and TSH levels (r = 0.44; P less than 0.01). Even though the duration of illness and TSH levels were similar in women with spontaneous disease with (n = 7) or without (n = 20) galactorrhea, the former were significantly younger (39.3 +/- 1.8 vs. 56.6 +/- 3 yr; P less than 0.001), and their PRL levels were significantly higher (69.3 +2- 8.9 vs. 42.9 +/- 2.2 ng/ml; P less than 0.001). The PRL response to metoclopramide in women with spontaneous disease was significantly smaller than that in controls (194 +/- 39% vs. 446 +/- 40%; P less than 0.001) and inversely correlated with basal PRL levels (r = -0.55; P less than 0.05). These data indicate that in primary hypothyroidism 1) the duration of illness is important in the development of hyperprolactinemia, 2) galactorrhea is more common in young women with spontaneous disease and high PRL levels, and 3) hypothalamic dopamine appears reduced in spontaneous disease.

[Bone mineralization and calcium intake in Chilean school children]. / Mineralización ósea e ingesta de calcio en escolares chilenos.

Bone mineralization was evaluated in 36 school age children with calcium intake below 50% of Recommended Dietary Allowances (RDA), and compared with 28 school age children with calcium intake higher than 100% of the RDA. The total group was aged between 86 and 178 months. The calcium intake was evaluated by 24 hours recordatory survey. Height for age and weight for height were evaluated according to WHO tables. Puberal development was evaluated according to Tanner stages. Bone mineral density (BMD) and total bone mass (TBM) of whole body, spine and femoral neck were measured with Norland 2600 densitometer. School age children with intakes below 50% of RDA had lower height for age adequation (97.7 +/- 4.0%), whole body TBM adequation (98.9 +/- 17.9%) and BMD adequation (97.8 +/- 7.9%) than those ingesting more than 100% of the RDA (115.9 +/- 17.4%), (109.7 +/- 18.0%) and (104.7 +/- 11.1%) respectively. In spine, however, there was a clear tendency to be lower, there were no significant differences between both groups. There were no differences in femoral necks BMD adequation, or TBM adequation between both groups. These results show that children with calcium intake below 50% of the recommendation has lower adequation of statural growth and bone mineralization. The role of calcium in the differences found in this study is discussed.

[Bone mineralization in adolescents suffering from postnatal malnutrition]. / Mineralización ósea en adolescentes que padecieron desnutrición postnatal temprana.

The bone mineralization of 6 male and 18 female adolescents with a mean age of 12 years and 11 months, who had suffered severe, early, postnatal protein-energy undernutrition, was analyzed. These patients have been followed up at our Institute since their nutritional rehabilitation. Bone mineralization was measured by bone dual isotopic densitometry (Gd 153). These results were compared with those of normal school-age Chilean children of the same age and sex. Weight for height of adolescent who had suffered from undernutrition was similar to the controls, and both were over 100% of the standard. Adequation of height for age was significantly less in those with previous history of undernutrition. Densitometries showed that adolescents with a past history of undernutrition had lower total bone mass in whole body, spine and femoral neck; differences disappeared when expressed per 100 cm of body height. There were no differences in bone mineral density in the different area measurements. It is concluded that the possible alterations that undernutrition produces in bone mineralization probably recover after nutritional rehabilitation, adequate nutritional follow up and health support.

[Bone mineralization in Chilean children determined by dual photon bone densitometry]. / Mineralización ósea en niños chilenos determinadas por densitometría ósea bifotónica.

In 198 school age children, aged 6 to 13 years, the bone mineral density (BMD) and total bone mass (TBM) was measured in total body, lumbar spine and hip, using a double beam photon densitometer with a Gd 153 source. An increase with age of BMD and TBM was found in all the analyzed areas. At 12 years of age, TBM and BMD of total body were higher in girls than in boys. BMD of lumbar spine was significantly higher in girls than in boys at ages between 11 to 13 years. BMD of lumbar spine and femoral neck of 9 years old females were 36% and 18% respectively, lower than values of young adult Chilean females. The importance of normal values of bone mineralization for the diagnosis of bone diseases and for the evaluation of programmes directed to solve this problems is emphasized.

[Bone mass in celiac patients]. / Masa ósea en pacientes con enfermedad celiaca.

Bone mineral content was measured in the whole body, the spine (L2-L4) and hip by Dual Photonic Absorpciometry (densitometer Norland 2600 Gd-153), in seventeen celiac patients, aged 6 to 12 years, with good adherence to the gluten free diet. The diagnosed was made before 30 months of age in 50% of cases. Average treatment duration was 69.8 +/- 36 months. The randomly selected control group was composed of 48 school age children, of the same age and sex of patients. Total bone mass (TBM) and bone mineral density (BMD) were expressed as Z scores on the basis of normal values established by the authors in Chilean children. Celiac patients had lower TBM and BMD of whole body, than controls (-1.11 +/- 0.94 vs 0.00 +/- 0.85 and -0.59 +/- 0.76 vs 0.06 +/- 0.84, respectively) and at the spine (-0.79 +/- 1.04 vs 0.003 +/- 0.92 and -1.49 +/- 0.99 vs 0.06 +/- 0.87 respectively). A lower TBM was founded at the hip (-0.62 +/- 1.28 vs -0.08 +/- 0.82) without differences in BMD. Celiac patients had a lower bone mass than controls despite early diagnosis and good compliance with the gluten-free diet. These differences could not be atributed entirely to the lower height of celiac patients. These results suggest that celiac patients constitute a risk group for development of osteoporosis later in life. This fact should be taken into consideration in the treatment of this condition.

[Osteoporosis in a man with idiopathic hypercalciuria, renal variety, treated with a hypocalcic diet]. / Osteoporosis en un hombre con hipercalciuria idiopática, variedad renal, sometido a dieta hipocálcica.

A 61 year old man with a calcic urinary stone at age 46 was submitted to a prolonged low calcium diet (about 400 mg/day). Normal serum calcium and elevated urinary Ca (725 mg/day were demonstrated). After a diet with a normal Ca content (900 mg/day) urinary excretion did not change. PTH, serum Ca and P were normal. Biphoton bone densitometry revealed severe osteopenia, with a spine density of 51% of normal. The addition of hydrocortisone (50 mg/day) reduced urinary Ca output over 25%; the addition of phosphate, 1125 mg/day, brought Ca output to normal levels. Thus, prolonged dietary restriction of Ca in the presence of high urinary Ca loss may produce severe osteopenia and osteoporosis.

[Treatment of anorexia nervosa]. / Tratamiento de la anorexia nerviosa.

Treatment of anorexia nervosa integrates psychiatric and medical aspects. Elements of analytically oriented (not true psychoanalysis) and behavioral forms of psychotherapy are utilized. Emphasis should be placed in the setting, patient-therapist relation, and alliance with the family. Weight gain is the gauge and one of the goals of the therapy, having in mind that as it increases anxiety may be generated. From a behavioral point some restrictions are indicated. Antipsychotic (or neuroleptic) and antidepressant drugs should be used. Haloperidol is the drug of choice among antipsychotics while amitriptyline is usually preferred as antidepressant. General medical measures include adequate nutritional support, limitation of physical activity, eventual supplementation with iron, folic acid and vitamin B12. Estrogen therapy associated to progestins, calcium and vitamin D should be considered to prevent osteopenia.

[Idiopathic tumoral calcinosis. A clinical case]. / Calcinosis tumoral idiopática. Caso clínico.

A 25-year-old Chilean woman of Jewish ancestry developed subcutaneous nodules at the thighs, axillae, elbows and coccygeal areas. X rays disclosed heavily calcified lesions at these levels. The patient's father had Whipple's disease, her mother and one brother had early hip osteoarthrosis and one son had idiopathic pancreatitis. Laboratory studies ruled out hyper or hypoparathyroidism. Electromyogram showed evidence of mild myopathy and inflammatory elements were present on muscle biopsy. However, the diagnosis of polymyositis associated to calcinosis was ruled out. Skin biopsy disclosed calcifications and fat necrosis. After 20 years of follow up, an increase in calcification specially at the pelvis and periarticular regions has been observed. Etiology, differential diagnosis and treatment are discussed.

[Epidemiology of fractures in Chile]. / Epidemiología de las fracturas en Chile.

Bone fractures represented 3.3% of diagnosis among 1,003,267 patients discharged from National Health System Hospitals in Chile during 1985. Among 73,534 certified deaths, 1.2% followed fractures. Significantly higher rates were observed in males; after age 75, fractures were more common in females. Rates per 100,000 for different fractures were: radio-cubital 45.4, shine and fibula 41, ankle 28.1, humerus 25.3, and hip 23.5. Among males the figures were shine and fibula 66.2, radius and cubitus 64.9, face 37.5 and ankle 37.1. Among females, hip 28.2, radius and cubitus 26.3, ankle 19.3 and humerus 16.5. Hip fracture is clearly related to age, the incidence raising from below 60 per 100,000 under age 60 to 617 in females and 330 in males above that age. Other fractures that increase with age include radius and cubitus, shine and fibula, ankle, humerus and femur.

[Cytokines, growth factors, and metabolic bone disease]. / Citoquinas, factores de crecimiento y enfermedad ósea metabólica.

Cytokines are polypeptides that bind to membrane receptors and may act in an endocrine, paracrine or autocrine way. Several cytokines and growth factors may be produced by bone cells, stored in the matrix or act on them. Osteoclasts derive from the bone marrow stem cell and, as monocytes, belong to the family of tissue macrophages. Their specific function is bone resorption. Interleukin 1, 6 and 11, transforming growth factor and tumor necrosis factor stimulate osteoclast mediated bone resorption. Interleukin 1 is the most potent bone resorption agent and seems to be identical to osteoclast activation factor, identified in multiple myeloma. The role of interleukin 1, 6, 11 and tumor necrosis factors in postmenopausal osteoporosis triggered by the fall in estrogen levels, has not been well defined yet. Cytokines that increase bone formation are insulin like growth factors I and II, transforming growth factor, platelet derived growth factor and bone morphogenic proteins. Probably, tumor necrosis factor and interferon-gamma have a depressor effect on bone formation. Cytokines and growth factors, liberated from bone cells or from the matrix during osteoclastic work, could be the signals responsible for coupling bone formation and resorption.

[Osteoporosis in men under 65 years old presenting as vertebral crushing: idiopathic or secondary? Study of 9 cases]. / Osteoporosis en hombres menores de 65 años manifestada por aplastamiento vertebrales: idiopática o secundaria? Estudio de 9 casos.

BACKGROUND: Osteoporosis in young or middle age men is unusual and requires an extensive diagnostic work-up. AIM: To report a retrospective review of nine men with osteoporosis. PATIENTS AND METHODS: The charts of nine men aged 27 to 61 years old (mean 39), that presented with a primary diagnosis of osteoporosis, were reviewed. RESULTS: Subjects were subjected to a diagnostic work up five years after the onset of symptoms. Their body mass index ranged from 21.7 to 26.3 kg/m2, all had vertebral fractures (crush fractures in 8 and a biconcave deformity in one) between T4 and L4 and all had normal serum calcium, phosphate, alkaline phosphatase and creatinine. Four patients had a history of nephrolithiasis and three had hypercalciuria. Bone density, measured in seven patients with a dual photon densitometer, showed a mean Z score of -2.0 in the spine and of -2.2 in the femoral neck. The final diagnoses of these patients were Cushing's disease in two, malabsorption syndrome in one, use of phenobarbital and hydantoin in one, overt renal hypercalciuria with low calcium intake in one and alcoholic liver disease in one. In three patients, osteoporosis was considered idiopathic. Of these, two had moderate absorptive hypercalciuria as a presumable risk factor. CONCLUSIONS: Six of the nine studied male patients with osteoporosis had an underlying cause and in three, this condition was considered idiopathic.

[Hematologic changes in anorexia nervosa]. / Las modificaciones hematológicas en la anorexia nerviosa.

We studied the hematologic values of 25 patients with anorexia nervosa. Age ranged from 12 to 38 years and 22 were females. Mean hematocrit was decreased to 36% and total leukocyte count to 4.400/microliters. Anemia was diagnosed in 13 patients. It was normocytic in 7 hypochromic microcytic in 7 and megaloblastic in 2. Seven of these anemic patients corrected their anemia with the treatment of anorexia nervosa, 3 required iron supplement and 2 folic acid. Bone marrow studies in 23 patients demonstrated hypoplasia in 17. Four patients had global bone marrow hypoplasia with decreased numbers of erythroblasts and megakaryocytes. A mucopolysaccharide substance substituted for a decreased fat content of bone marrow. A decreased bone marrow reserve of neutrophils and their margination in blood vessels contributed to leukopenia, which was not associated to an increased number of infections. Blood coagulation tests and platelet aggregation were normal.

[Twelve-year trends of hip fracture rates in Chile. Is there a relationship between their increase and population aging?]. / Tendencia de las tasas de fracturas de cadera en 12 años en Chile: aumento independiente del envejecimiento poblacional?

BACKGROUND: Epidemiology of osteoporosis is assessed measuring bone density or measuring the rates of bone frailty-related fracture rates. Of these, the most important are hip fractures, that markedly increase after 65 years of age. AIM: To measure the incidence of hip fractures in Chile from 1982 to 1993. MATERIAL AND METHODS: All hospital discharges that occurred in Chile from 1982 to 1993 were analyzed, looking for the diagnosis of hip fracture. National censuses in the same period were also analyzed searching for possible changes in the age structure of the population. Fracture rates were analyzed for three age groups, and changes along the years were calculated correlating the rates with the number of the year. RESULTS: In the twelve year period, women aged 55-64 years old had a correlation of 0.32 (NS), women aged 65-74 years old had a correlation of 0.58 (NS) and women aged over 75 years old had a correlation of 0.95 (p < 0.001). This age group corresponded to 2.01% of the whole population in 1982 and to 2.52% in 1993. The mean age of the group increased from 80.7 to 80.9 years in the same lapse. CONCLUSIONS: Fracture rates increased in the 12 years period studied, specially among women older than 75 years old. During the same period the proportion of people over 75 years old also increased, but there was only a slight increase in its mean age. Thus, the increase in fracture rates is disproportionate to population aging and could be related to changes in lifestyles.

[Primary hyperparathyroidism caused by a mediastinal adenoma with intermittent hypercalcemia and severe bone disease]. / Hiperparatiroidismo primario por adenoma mediastínico, con hipercalcemia intermitente y enfermedad ósea acentuada.

We report the case of a 33-year-old woman who was operated on with the diagnosis of primary hyperparathyroidism (PHP) in 1986. She had bone disease and slight hypercalcemia. Two parathyroid glands were removed with a lack of clinical improvement. Subsequently, the serum calcium levels were normal with occasional slight increases. Depressed phosphorus values and elevated alkaline phosphatases and PTH levels were also present, associated with severe bone involvement and muscular weakness. A second cervical exploration performed in 1989 disclosed only a normal parathyroid gland, which was not removed. In 1990, a thoracic CT scan showed the presence of a 1 cm mediastinal nodule close to the great vessels. A thoracotomy was performed to remove this nodule, which proved to be a parathyroid adenoma. After surgery, the patient presented with a "hungry bone" syndrome, characterized by very low levels of calcium, phosphorus and magnesium, which required enteral and parenteral calcium and magnesium supplements, plus dihydroxyvitamin D. The association of normocalcemia and intermittent hypercalcemia with severe bone disease is very rare, as is the presence of a mediastinal adenoma. This could explain the difficulty in the diagnosis in this case.

[Plasma calcium levels in critical patients with and without sepsis]. / Niveles de calcio plasmático en pacientes críticos con y sin sepsis.

We determined total plasma calcium levels in 44 critically ill patients without evidence of renal or hepatic failure, 25 of them with active systemic infection. Plasma Ca was 7.49 +/- 0.1 mg/dl in the septic group compared to 8.46 +/- 0.2 in non septic patients (p < 0.01). Corresponding levels of serum albumin were 2.26 +/- 0.1 and 3.05 +/- 0.2 milligrams, respectively (p < 0.01). Corresponding corrected plasma Ca levels were 9.19 +/- 0.1 and 9.39 +/- 0.1 mg/dl (NS). No correlation of lactate and plasma Ca levels was found. Mortality was 56% for septic and 16% for non septic patients. Patients with hypocalcemia had 53% mortality rate compared to only 16% in normocalcemic patients. PTH levels were normal in all but one patients, thus ruling out a rapid installation secondary hyperparathyroidism. Hypoperfusion does not appear related to ionic Ca levels given the lack of correlation of Ca and lactate levels. Mortality is related to sepsis and hypoalbuminemia but not to corrected Ca plasma levels.

[Density and bone mineral content and their relation to anthropometric parameters in a normal Chilean population. A study with women]. / Densidad y contenido mineral óseo y su relación con parámetros antropométricos en población normal chilena. Estudio en mujeres.

We studied 227 normal women from 20 to 89 years of age. Bone density and mineral content was measured in vertebral bodies L2 to L4, both femurs and whole body, using a double beam photon densitometer with a 153Gd source. Body height remained between 156 and 158 cm up to age 64, then decreased gradually to 152 cm. Weight increased from age 35 to 69 (mean 9 kg) and then decreased. Mean bone density of the lumbar spine was 1.07 g/cm3 up to age 50. A marked decrease in density was observed for 10 years after that age, gradually slowing in later years. Mean density of the femoral neck was 0.931 g/cm3 up to age 50. A steady decline is observed in later ages down to 0.763. The density ratio of spine to femoral neck remains under 1.2 up to age 60, then increases progressively. Total mineral content, absolute or relative to body weight, was a less sensitive index. Total content decreased from above 2000 gm to about 1550 gm after age 70. The greater proportion of mineral contents is found in the lower extremities (30%). With increasing age a greater mineral loss was observed in the trunk, including spine and hips, compared to other segments. Our findings reveal bone densities somewhat lower than those reported from USA and higher than those reported from Denmark.

[Active acromegaly and gigantism: some clinical characteristics of 50 patients]. / Acromegalia y gigantismo activos:algunas características clínicas de 50 pacientes.

50 patients with autonomous growth hormone excess (48 with adult acromegaly and 2 with gigantism) were studied between 1966 to 1986 (2.38 pts/year). Characteristic clinical presentation, an increase in growth hormone (GH) uninhibited by glucose, and/or hyperphosphemia and hyperhydroxiprolinuria were present in all patients. No cases of hypercalcemia were recorded. Phosphemia was increased in 55.8%, alkaline phosphatases in 61.7%, calciuria in 26.9% and hydroxyprolinuria in 74.2% of the patients. Basal GH was over 5 ng/ml (89.9 DS +/- 170.9) in 42 pts, and in 37 was not suppressed after glucose administration, 38% had an increased (paradoxical response) and 62% a flat response (less than 50% change of basal values). TRH test was performed in 14 patients, 8 presented an increase in GH titer. Hyperprolactinemia was seen in 4 of 12 patients in whom this hormone was measured. The size of the sella turcica was increased in 93%, and although the larger sellar size correlated to higher levels of GH, correlation was not significant. 20% of the pts had rheumatological disease, 14% goiter, 12% cardiac disease, 26.5% had diastolic hypertension and 4% renal lithiasis (hypercalciuric pts). 38% had hyperglycemia with a diabetic glucose tolerance test and 18% had non-diabetic abnormal glucose tolerance test.