Spontaneous postoperative normalization of growth hormone levels in two patients with acromegaly not cured by transsphenoidal surgery.

Postoperative persistence of elevated growth hormone (GH) levels in patients with acromegaly usually suggests residual adenoma tissue secreting GH and is an indication for further treatment. In rare cases, spontaneous normalization of serum GH levels in patients with acromegaly has been reported to occur as a consequence of intratumoral hemorrhage (pituitary apoplexy). We report two patients in whom persisting acromegaly was documented 1 and 2 weeks, respectively, after transsphenoidal operation and who experienced spontaneous normalization of GH levels. In one patient, this favorable outcome was found 1.5 years after the operation and followed a pregnancy. The other patient, whose GH values normalized 3 months after operation, had received preoperative treatment with a new, long-acting somatostatin analog.

The different types of hyperthyroidism in Europe. Results of a prospective survey of 924 patients.

In a prospective multicentric study, 924 untreated hyperthyroid patients were investigated, coming consecutively within one year into 17 thyroid centers of 6 European countries. With the aid of clinical information, evaluation of thyroid scan and centrally assayed thyroid hormones, thyroid antibodies, TSH-binding inhibiting immunoglobulins (TBII), and urinary iodine, different types of hyperthyroidism could be shown. Two types of hyperthyroidism could be defined directly: autonomous adenoma in cases of hot nodules in thyroid scan and Graves' disease, defined as hyperthyroidism with eye symptoms, and/or measurable TBII levels. The remainder, called "non-classifiable", included TBII negative Graves' patients, comprising of Hashitoxicosis, toxic nodular goiter, and other multifocal autonomies. 9.2% of the patients had an autonomous adenoma, 59.6% Graves' disease, and 31.2% unclassified hyperthyroidism. The main and significant difference between these types were mean age, goiter size, nodularity, and severity of the disease, being especially expressed in Graves' disease. Graves' patients had significantly increased T3/T4 ratios. Using as additional criteria diffuse regular uptake and/or increased T3/T4 ratios for immunogenic types of hyperthyroidism at least half of the 31.2% unclassified hyperthyroidism are probably Graves' disease. Forming two groups of iodine-deficient areas (IDA) and iodine-sufficient areas (ISA) according to the urinary iodine, it was possible to elucidate some characteristics independently of local factors. Autonomous adenoma was more frequent in IDA (10.1%) than in ISA (3.2%). Differences in iodine supply are reflected in the three types of hyperthyroidism by a significant higher prevalence of goiter, thyroid nodularity, lower thyroid hormone concentrations, and a higher rate of T3 toxicosis in IDA.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex-related differences in hematological values. A study on the erythrocyte and granulocyte count, plasma iron and iron-binding proteins in human transsexuals on contrasexual hormone therapy.

Hematological data known or supposed to be influenced by individual sex hormones were evaluated in 18 untreated transsexuals (TS) and in 20 castrated or non-castrated TS on androgen and estrogen treatment, respectively. Profiting from a situation of clinically controlled hormonal sex-transformation it was tested, whether the circulating erythrocyte and granulocyte mass and iron metabolism are linked to a male and female sex-hormone constellation. The erythrocyte and granulocyte counts were significantly higher in untreated males and treated female-to-male TS than in untreated females and treated male-to-female TS. The unexpected finding of sex hormone-dependent granulocyte fluctuations was corroborated by parallel concentration changes of lactoferrin, a granulocyte-derived plasma protein. Iron metabolism as judged from plasma iron, total iron-binding capacity and serum ferritin was unaffected by sexual transformation. Plasma iron and the total iron-binding capacity did not differ significantly in untreated and treated TS of either type. The serum ferritin concentration, however, was significantly lower in untreated as well as in virilized females than in untreated and in feminized males, but was not significantly changed by long-term androgen or estrogen treatment. The present study demonstrates the potential of human transsexualism as a model for the study of sex-related biological processes.

[Clinical aspects of hyperthyroidism in areas of different supplies of iodine. Results of a European prospective study]. / Klinische Aspekte der Hyperthyreose in Gebieten unterschiedlicher Jodversorgung. Ergebnisse einer europäischen prospektiven Studie.

Clinical aspects of 924 unselected patients with hyperthyroidism from 17 thyroid centres of 6 European countries were investigated in a prospective study for exactly 1 year. Serum samples were centrally assayed for thyroid hormones, thyroid autoantibodies and TSH-binding inhibiting immunoglobulins (TBII), and urine samples for iodine. 26 items of information per patient were computerized and evaluated. Forming 2 groups from iodine-deficient areas (IDA) and iodine-sufficient (ISA) according to the urinary iodine, it was possible to elucidate some characteristics independently of local factors. The most important findings were: 1. Three types of hyperthyroidism were described: Graves' disease was defined as hyperthyroidism with eye symptoms and/or the presence of measurable TBII; autonomous adenomas were defined by a single hot nodule in the thyroid scan; the remainder included TBII negative hyperthyroid patients as well as non-immunogenic forms of hyperthyroidism (toxic multinodular goiter and other multifocal autonomies). These were termed "non-classifiable" patients. Graves' patients, representing an average of 60% of the patients, have an age peak between 40 and 49 years; they are 10 years younger than unclassified hyperthyroid patients and 20 years younger than patients with autonomous adenoma, who represented 9.2% of the patients. Surprisingly, there was no difference in the prevalence of Graves' disease between IDA and ISA. 2. An unexpectedly high rate of 10.5% of hyperthyroid patients (Graves' disease 8.5%, non-Graves' disease 14.2%) had no goiter, a figure increasing in the elderly to almost 17%. In IDA the thyroid was larger and the goiter more often nodular than in ISA. IDA are characterized by significantly higher rates (11.3%) of autonomous adenoma than ISA (3.2%). 3. 59.4% of 507 patients with Graves' disease had eye symptoms, 44.6% of at least grade II or higher using the Werner classification. There was no difference between patients from ISA and IDA. We found unilateral ophthalmopathy in 6.7% of Graves' patients. 4. The median iodine excretion was calculated from urinary iodine after exclusion of values over 250 micrograms iodine/g creatinine, arbitrarily defined as iodine contamination. In IDA the median iodine excretion was 63.6, and in ISA 105 micrograms/g of creatinine. 5. Surprisingly, proven iodine contamination was as frequent in IDA (14.5%) as in ISA (15.2%). In the survey protocol, however, this was noticed less often by physicians in ISA.(ABSTRACT TRUNCATED AT 400 WORDS)

Endocrine manipulation of meningiomas with medroxyprogesterone acetate. Effect of MPA on receptor status of meningioma cytosols.

Fifteen patients with intracranial or spinal meningiomas have been treated with the semisynthetic progestational agent medroxyprogesterone acetate (MPA, Depo-Provera) prior to surgical removal of the tumors in order to investigate the influence of MPA on the progesterone receptor (PR) status of meningioma cytosols. MPA acted as a competitive binder to meningioma-PR: The mean PR values were 15.6 fmol/mg protein (range 0-69) and 338.3 fmol/g tumor (range 0-1190), respectively. In comparison, mean PR values of our untreated meningioma series (n = 58) were 54.9 fmol/mg protein (range 0-586) and 2813 fmol/g tumor (range 0-17,168), respectively. In cases of two-stage resection of meningiomas MPA significantly decreased PR activity in the cytoplasm of meningioma cells. We conclude that MPA binds to meningioma PRs, however, its effect on the growth rate of meningiomas has still to be elucidated.

[Findings: small testicles]. / Befund: kleine Hoden.

Small testicles are normal in prepubertal boys, irrespective of their height and weight. Small testicles associated with premature sexual development (pseudopuberty) usually reflect an alternate source of androgens, most frequently adrenal (e.g. in congenital adrenogenital syndrome). Small testicles as a result of testicular atrophy are either the consequence of a painful event such as mumps-orchitis or trauma (such as torsion), or a side effect of extratesticular disease (such as liver cirrhoses, chronic alcoholism, haemochromatosis, Curschmann-Steinert dystrophic myotonia etc.). Certain drugs (e.g. immunosuppressive and chemotherapy) and irradiation may also lead to testicular atrophy. Cryptorchidism as the expression of prenatal testicular damage may lead to an "incompetent", i.e. small, testis even if properly descended by surgery. However, a small testis after orchidopexy may also be the consequence of injury to blood vessels during surgery. The cryptorchid testis has an increased though still low incidence of malignancy, but a markedly elevated rate of sterility. Probably the most frequent cause of small testicles is Klinefelter syndrome (XXY/47), involving a wide spectrum from eunuchoid hypogonadism to a normally virilized albeit sterile male, in whom gynecomastia is not much more frequent than in the average male population but in whom the mammary cancer risk is definitely elevated almost to female rates.

[Polyneuropathy, organomegaly, endocrinopathy and skin changes in a case of solitary myeloma]. / Polyneuropathie, Organomegalie, Endokrinopathie und Hautveränderungen bei einem Fall mit solitärem Myelom.

The case is reported of a 32-year-old woman with polyneuropathy, organomegaly, edema, endocrinopathy, dark skin and solitary myeloma with monoclonal gammopathy of IgG/lambda type. More than 100 cases of this rare disorder have been observed up to now, mainly in Japan. In recent reviews the terms POEMS-syndrome or Crow-Fukase-syndrome have been used. Local radiotherapy of the myeloma led to lasting regression of symptoms. Studies with immunocytochemistry and immunoelectroblotting revealed specific antibody activity against hypophysis, suggesting that the pathologic monoclonal myeloma antibodies may damage the neuroendocrinic centers in hypothalamus and hypophysis as the primary target. Most of the multisystemic symptoms would thus be explained as secondary alterations.

[Hyperprolactinemia]. / Hyperprolactinämien.

Hyperprolactinemia is frequent in clinical endocrinology. Its commonest causes are, besides pregnancy and lactation, drugs, mainly involving the generally used psychopharmaca and the equally ubiquitously prescribed estrogens. The single most important cause is a pituitary tumor, the prolactinoma, but lesions of the hypothalamus or pituitary stalk, primary hypothyroidism, liver cirrhosis and chronic renal failure, among others, may also provoke hyperprolactinemia. The clinical features of hyperprolactinemia in women are mainly amenorrhea, or irregular menses, galactorrhea, hirsutism, infertility and loss of libido. In men loss of libido and/or impotence are the most important symptoms, accompanied by infertility. Macroadenoma, more frequently seen in men than in women, may cause tumor symptoms such as headache and ophthalmologic disorders (visual field loss). The main biochemical finding is hyperprolactinemia, which should be repeatedly checked. In general, high concentrations are mainly found in large adenomas, while microadenomas usually involve only mild hyperprolactinemia, though there are numerous exceptions. While dynamic tests of prolactin secretion have provided useful information about the pathophysiology of prolactin secretion, their use in routine clinical work is controversial and of limited value. As a routine neuroradiological examination, high resolution CT of the pituitary area is to be recommended. In all hyperprolactinemic patients with suspicion of macroadenoma, ophthalmologic evaluation of fundus and visual fields should be performed. Dopaminergic drugs such as bromocriptine rapidly reduce serum prolactin levels in hyperprolactinemic women and men with micro- or macroadenoma. With these drugs considerable tumor shrinkage is possible.(ABSTRACT TRUNCATED AT 250 WORDS)

[Therapeutic results in hyperthyroid patients from the Bern endemic goiter region]. / Therapieresultate bei hyperthyreoten Patienten aus dem Berner Kropfendemiegebiet.

Among 239 hyperthyroid patients from the Bernese endemic goiter area referred to specialist, 66% were found to have Graves' disease (MB), 12% hyperthyroid autonomous adenoma ( AAH ) and 22% multinodular toxic goiter (HK). 189 (79%) of these 239 patients have been followed up 5.4 +/- 3.8 years after the last treatment. At the time of follow-up, 146 patients (77%) were euthyroid without additional treatment. 97 of these (51%) became euthyroid after a single, initial treatment (41% of the MB, 83% of the AAH and 67% of the HK). 68 patients (36%) developed recurrences, in some cases several (48% of the MB, 4% of the AAH and 15% of the HK). These recurrences occurred in 56% of cases treated with carbimazole, in 19% of the thyroidectomies and in 11% of the radioiodine treated cases. 30% of the recurrences occurred two or more years after the last treatment. At the time of follow-up, 40 patients (21%) were found to be hypothyroid (23% of the MB, 13% of the AAH and 21% of the HK). However, only 20 of these patients had been treated properly with 1-thyroxin; the other 20 were either insufficiently treated or not at all. Hypothyroidism has been observed in 27 (25%) patients after thyroidectomy and in 13% (23%) patients after radioiodine. No complications were recorded after radioiodine or under carbimazole treatment. After surgery, 2.8% of the patients had recurrent nerve palsy and 2.8% permanent hypoparathyroidism. The present data are in accordance with those published from outside the goiter areas.(ABSTRACT TRUNCATED AT 250 WORDS)

[Place of nuclear medicine methods in thyroid diagnosis]. / Der Platz der nuklearmedizinischen Methoden in der Schilddrüsendiagnostik.

Since the introduction of precise and easily accessible methods of measuring the level of T4 and T3 in serum, the use of isotopes to assess thyroid function can no longer be advocated. Moreover, the recent growth in knowledge concerning the pathogenesis of thyroid diseases indicates that not even scintigraphic imaging of the thyroid gland contributes substantially to therapeutic decisions in routine situations such as Graves' disease and most euthyroid and hyperthyroid nodular goiters. The use of isotopes in clinical thyroidology should therefore be restricted to the fairly few cases where it is essential for diagnostic and therapeutic decisions, such as, for example, in planning 131I-therapy of postoperative goiter recurrences. A critical review of the indications is presented. Isotopes continue, however, to expand our knowledge of the pathogenesis of thyroid diseases in clinical research.

Evaluation of endocrine ophthalmopathy with saccadic eye movements.

Horizontal saccades were examined in 25 patients with hyperthyroidism and/or endocrine ophthalmopathy (EOP) using the infrared reflection method. With one exception none had restriction of horizontal eye movements. Conventional saccadic parameters were usually normal. A standardized test for muscle fatigue, however, gave pathological results in all but one of the patients with EOP, and also in three of seven patients with hyperthyroidism but no clinical EOP. In one of the latter the oculographic abnormality disappeared with treatment, while another developed clinical EOP. Performing a saccadic fatigue test seems to be useful for detecting early EOP and especially for monitoring its course.

[Autonomy and heterogeneity of the follicle in euthyroid and hyperthyroid human nodular goiter: answer to old riddles?]. / Autonomie und Heterogenität der Follikel in der euthyreoten und hyperthyreoten menschlichen Knotenstruma: die Lösung alter Rätsel?

The mechanisms responsible for the transformation of a morphologically and functionally normal thyroid into a heterogeneous eu- or hyperthyroid nodular goitre are summarized. The 3 basic processes of goitre pathogenesis are: 1. Each goitre develops from a normal thyroid gland by generation of new follicles. 2. New follicles are formed by multiplication of preferentially replicating cell clones of the follicular epithelium. Follicles already begin multiplying in response to a goitrogenic stimulus too weak to enhance metabolic functions other than replication. 3. The epithelial cells of normal follicles are not homogeneous and monoclonal, but belong to different populations with different metabolic equipment. Therefore, the daughter follicles may be metabolically different, e.g. in iodinating capacity. A certain degree of autonomous, i.e. TSH-dependent function is inborn to all follicles. The individual degree of autonomy of iodine turnover is not variable during goitrogenesis but determined by the metabolic individuality of the mother cell at the moment of folliculoneogenesis. These three basic processes explain the typical heterogeneity of nodular goitre. From autonomous highly iodinating cell families, autonomous "hot" daughter follicles arise which may be scattered all over the gland either as single follicles or as clusters of varying size (so-called "disseminated autonomy"). Particularly large clusters of "hot" follicles result in scintigraphically visible hot nodules, often called "toxic adenomas". Hyperthyroidism appears when the total joint autonomous hormone production of normal and "hot" follicles exceeds the requirements of the organism. The large majority of goitre nodules, including the so-called "toxic adenoma", are not true monoclonal benign neoplasias. Rather, they are built up by the same polyclonal heterogeneous follicles as extranodular goitre tissue. They have no choice but to expand in nodular fashion because they replicate within a poorly extensible network of connective tissue. This network of fibrous tissue results from scarring of multiple hemorrhagic necrosis occurring episodically during goitre growth.

[Bromocriptine therapy]. / Bromocriptintherapie.

1. The study of bromocriptine and its effects has opened up new perspectives on the highly sophisticated neuroendocrine control mechanisms and the role of neurotransmitters. 2. As a specific prolactin inhibitor, bromocriptine is the treatment of choice in many cases of hyperprolactinemia in female and male. There is ample evidence that with bromocriptine a reduction of pituitary tumor size (particularly in prolactin-secreting tumors) can be achieved. 3. One highly specific use of bromocriptine, and which involves virtually no problems, is inhibition of puerperal lactation. 4. Bromocriptine is effective and useful in the treatment of acromegaly. While it may restore growth hormone levels to normal in mild and selective cases, it may be helpful in controlling severe cases in which surgical or radiotherapeutic approaches have failed to achieve satisfactory results. 5. As a dopamine agonist, bromocriptine offers a new possibility of treating parkinsonism. It may be given alone or, as is preferable in many cases, in combination with submaximal doses of levodopa. 6. Side effects are sometimes only observed on initiation of bromocriptine therapy, sometimes occur only during chronic therapy, and may occasionally necessitate interruption of the treatment. Sometimes continuation of therapy leads to tolerance of unwanted effects. Patients should be informed before the start of bromocriptine treatment about the possibility of side effects. With proper instruction on the manner in which the drug should be taken, many adverse reactions can be avoided or diminished.