[A 46-year-old patient with atrial fibrillation, elevated thyroid hormones and normal thyrotropine]. / Vorhofflimmern, erhöhte Schilddrüsenhormone und nicht supprimiertes TSH bei einem 46-jährigen Patienten.

We report on a 46 year old patient with a history of paroxysmal atrial fibrillation who presented to our emergency room. Diagnostic evaluation showed elevated free peripheral thyroid hormone levels and thyrotropine (TSH) hormone within normal limits. Ultrasound of the thyroid was normal, and thyroid autoantibodies were found in the normal range. There was a positive family history for thyroid dysfunction. TSH-producing adenoma (TSHoma) of the pituitary gland - the main differential diagnosis - was excluded by cranial MRI and laboratory tests. Familial thyroid hormone resistance (Refetoff syndrome) was suspected and could be confirmed by detection of a pathogenic mutation within the beta-thyroidhormone receptor gene. After spontaneous conversion to sinusrhythm the patient was treated with a beta(1)-selective betareceptor blocker. Up to now, no specific treatment is available to correct the defective beta-thyroidhormone receptor.

The effect of acute application of pegvisomant alone and in combination with octreotide on endogenous GH levels during a 6-h test in patients with acromegaly on constant pegvisomant treatment.

OBJECTIVE: Co-treatment with somatostatin analogues and growth hormone receptor antagonists in acromegaly might be a new treatment option abolishing the negative effects of monotherapy. Nevertheless, little is known about the acute effect of the combined treatment on endogenous GH and pegvisomant levels. DESIGN: Ten acromegalic patients on constant pegvisomant therapy were included. Two 6-h GH secretion profiles were performed once after pegvisomant alone (P), the other after an additional 100 microg octreotide sc injection (PO). After 180 min, all patients received a standardized light mixed meal. Endogenous serum GH and pegvisomant levels were measured by special in-house assays. In addition, insulin and glucose were measured. RESULTS: In the combined profile PO, a significant decrease of median endogenous GH was seen (p<0.01, median percentage decline 75.2%, range 23.7-88.2), which was not seen in profile P. Seven of 10 patients had a decline >70% and might be seen as responders. After meal, endogenous GH significantly decreased only in profile P (p<0.01). Pegvisomant levels did not differ significantly between profiles and did not change significantly during the tests. After meal, glucose levels rose higher and later and insulin levels lower and later in profile PO than in profile P. CONCLUSION: During pegvisomant treatment, endogenous GH can be reduced significantly by acute application of a somatostatin analogue. Therefore, in acromegalic patients on pegvisomant therapy GH regulation due to somatostatin analogues seems to be preserved.

[Pharmacotherapy of pituitary diseases]. / Medikamentöse Therapie von Hypophysenerkrankungen.

Successful pharmacotherapy of pituitary hormonal excess is established only in the treatment of acromegaly (dopamine agonists, somatostatin analogues, GH-receptor-antagonists) and of prolactinomas (dopamine agonists). Gold standard in the treatment of acromegaly is transsphenoidal pituitary surgery, while in prolactinomas, surgery is indicated only in exceptional cases. Substitution of pituitary insufficiency offers the patients a normal quality of life. Substitution of the cortico- and thyrotrope axis with hydrocortisone and levothyroxine is vital. In women, substitution of the gonadotrope axis should be performed up to menopause (estrogen/gestagen). In men, substitution should be performed lifelong (trans-dermal testosterone body patches, testosterone gel, testosterone undecanoate/enanthate). To achieve fertility, gonadotropins or pulsatile GnRH therapy has very good results. Especially in younger patients, substitution of growth hormone may be useful (somatropin).

Gamma-knife surgery is effective in normalising plasma insulin-like growth factor I in patients with acromegaly.

OBJECTIVE: For patients in whom acromegaly persists despite pituitary surgery or drug treatment, gamma-knife surgery represents an additional treatment option. Considering carefully the different reported biochemical outcomes, the central point is whether gamma-knife radiosurgery has advantages compared to conventional radiotherapy or, furthermore, to newer medical therapies, such as long-acting somatostatin analogues or growth hormone receptor antagonists. DESIGN AND METHODS: We report the outcome of 44 patients with acromegaly, who received gamma-knife surgery with the Leksell gamma knife. The median follow-up time was 1.9 years (0.5-4.3 years) post-radiosurgery. 43 of 44 patients had previously undergone pituitary surgery. RESULTS: Immediately prior to gamma-knife surgery, median xULN of patients' serum IGF-I was 1.9 times above upper limit of normal (range: 0.5-8.9 xULN [multiple of upper limit of normal range]). There was a significant decline of serum IGF-I at patients' final follow-up. We found a normal age-adjusted IGF-I in 21/44 patients (xULN of IGF-I<1). Furthermore, as the number of treated patients increased, we found an improvement in remission rate, which let us assume that there was a learning effect for the gamma-knife performing team over time. In addition, the median adenoma size decreased from 1.5 ml (0.1-6.9 ml) prior to gamma-knife therapy to 0.3 ml (no rest vol. detectable-2.4 ml) at patients' last visit. CONCLUSION: We have shown that pituitary gamma-knife surgery is effective in lowering serum IGF-I levels. At the end of the follow-up period, 48 % of our cohort had normal age-adjusted IGF-I levels.

Four-year follow-up of acromegalic patients treated with the new long-acting formulation of Lanreotide (Lanreotide Autogel).

Lanreotide Autogel (Ipsen) is a long-acting somatostatin analogue (SA) in a new galenic formulation suitable for subcutaneous (s.c.) injection. In our department, 11 patients with therapy-resistant acromegaly were treated with Lanreotide Autogel for 48 months. 10/11 patients had previously undergone transsphenoidal surgery. For a median duration of 1.4 years prior to Lanreotide Autogel, the patients received Lanreotide PR 30 mg every 7, 10, or 14 days. 60, 90, or 120 mg of Lanreotide Autogel was administered by deep s.c. injection every 28 days, with the higher dosage being given to those with the previously shortest injection interval under Lanreotide PR. Dose was adjusted on the basis of Growth Hormone (GH) level after 4, 8, and 12 months with a minimum dose of 60 mg and a maximum dose of 120 mg. The efficacy of Lanreotide Autogel treatment was evaluated by measuring GH concentrations (4 hour profiles) and IGF-I levels. Before switching to Lanreotide Autogel, the multiple of the upper limit of normal (xULN) of IGF-I levels was 1.2 (median) and the median GH level was 1.3 microg/l. 3 out of 11 patients had an IGF-I within the age- and sex-adjusted normal range. After 48 months of treatment with Lanreotide Autogel, six patients had an IGF-I within the normal range. Median GH levels were at 1.3 microg/l and xULN of IGF-I was at 1.0 compared to Lanreotide PR 30 mg treatment (p < 0.001). At the end of the study, 8 patients received 120 mg Lanreotide Autogel, 2 patients 90 mg and 1 patient 60 mg, respectively. There was slight but significant deterioration of glucose metabolism with an increase of HbA1c. In conclusion, the new galenic formulation of Lanreotide improves not only the control of biochemical markers of acromegaly compared to the conventional PR formulation, but is also easier to administer given its deep s.c. method of administration. Glucose metabolism has to be followed carefully in patients on high-dose Lanreotide Autogel.

[Therapy of pituitary diseases. What can be achieved with medication and hormones?]. / Therapie hypophysärer Erkrankungen. Was Sie mit Medikamenten und Hormonen erreichen können.

Pharmacotherapy is available only for pituitary adenomas producing growth hormone and prolactin (acromegaly, hyperprolactinemia). While dopamine agonists and somatostatin analogues are usually administered to acromegaly patients only after unsuccessful surgery, dopamine agonists are the treatment of choice in patients with prolactinomas. Replacement treatment in patients with insufficiency of the anterior lobe of the hypophysis is oriented to the extent of the deficits. Theoretically, replacement treatment can be applied for any functional loss. Of essential importance is the replacement of lost adrenal cortical function by the regular administration of physiological doses of hydrocortisone, and of lost thyroid function by the administration of L-thyroxine. In high-stress situations, for example, due to severe illness, the hydrocortisone dose must be increased significantly, and if necessary given parenterally. Gonadal function is replaced either with gonadal steroid hormones or gonadotropin or GnRH in patients wishing to have children. In adults, replacement of growth hormone is also indicated to decrease cardiovascular risk. This, however is very expensive and requires s.c. injections.

Conventional pituitary irradiation is effective in normalising plasma IGF-I in patients with acromegaly.

OBJECTIVE: For patients in whom acromegaly persists despite pituitary surgery, conventional pituitary irradiation represents an additional treatment option. A 30-60% cure rate is described in the literature, but these studies did not utilise strict rules of remission, such as "safe" GH levels <2.5 microg/l, and age-adjusted normal IGF-I levels. DESIGN AND METHODS: We report the outcome of 41 patients with acromegaly who received pituitary conventional external irradiation. The median follow-up time was 12.8 years (3.7-43.4 years) post-radiotherapy. RESULTS: The median pre-irradiation GH level was 31.0 microg/l (7.0-210 microg/l). Information on IGF-I levels was only available for 6 patients prior to therapy. Utilising strict rules of remission, one-third (14/41) of our patients had normal biochemical parameters, i.e. "safe" GH (0.5 microg/l (range 0.2-1.6 microg/l)) and normal age-adjusted IGF-I levels (multiple of upper limit of normal range (xULN); 0.45 (0.2-1.0)) at the end of the follow-up period. An additional 9 patients achieved normal levels with adjunctive drug therapy. Furthermore, disease activity was reduced in a considerable proportion of the 18 patients who did not achieve normal biochemical levels (GH: 3.6 microg/l (1.9-15.7 microg/l); xULN of IGF-I: 1.6 (0.9-2.6)). In retrospect, remission is unlikely in patients who had a GH level greater than 52 microg/l (mean+2 s.d. of cured patients) prior to radiotherapy. In addition to the 12 patients with pre-irradiation pituitary functional deficiency, another 11 patients developed symptoms of panhypopituitarism during the 3-year period following irradiation. Within a 6-year period, partial pituitary insufficiency was observed in a further 7 patients, thus necessitating hormone substitution treatment. CONCLUSION: Using strict rules of remission, in our cohort we found both a normalisation of IGF-I and safe GH levels in 34% of patients treated for acromegaly with conventional irradiation therapy.