Treatment of severe life threatening hypocalcemia with recombinant human teriparatide in patients with postoperative hypoparathyroidism - a case series.

INTRODUCTION: Hypocalcaemia is a common postoperative complication, both after the resection of parathyroid adenoma associated with primary hyperparathyroidism and after total thyroidectomy due to thyroid cancer or nodular goitre. For a few years, in patients with postoperative hypoparathyroidism and severe hypocalcaemia, who cannot discontinue intravenous calcium preparations even with the use of high vitamin D doses, attempts have been made to add recombinant human parathormone (rhPTH) to the treatment schedule. In this work, for the first time in Poland, we demonstrate the potential use of teriparatide for the treatment of severe hypocalcaemia based on three different cases of postoperative hypoparathyroidism. MATERIAL AND METHODS: Case 1. Female (52) with postoperative hypoparathyroidism, after total thyroidectomy and the removal of lower left parathyroid gland due to hyperparathyroidism, several weeks after the surgery still required intravenous calcium infusions because of tetany symptoms. Just one month of teriparatide treatment at 20 µg/0.08 mL given in daily subcutaneous injections proved sufficient to control calcium levels with oral calcium and vitamin D preparations during the next few days until total resolution of hypocalcaemia symptoms and the achievement and maintenance of laboratory normocalcaemia in the following weeks. CASE 2: Female (33) with hypoparathyroidism following total thyroidectomy in 1996 because of papillary thyroid cancer, with congenital tubulopathy associated with renal loss of calcium and magnesium, and the symptoms of tetany recurring since the day of surgery, requiring intravenous calcium administration every 2-3 days. Currently, the patient has been hospitalised because of venous port infection, the only venous access, which made intravenous therapy impossible. Because of the life-threatening condition of the patient, bridging teriparatide treatment was prepared (20 µg/0.08 mL). Complete resolution of clinical symptoms of hypocalcaemia was obtained with teriparatide doses given every 8-12 hours, which made dose reduction possible. Case 3. Female (52) after major oncological surgery because of laryngopharyngeal and cervical oesophageal cancer with the removal of parathyroid glands, fed through PEG, was admitted to hospital with the symptoms of tetany. Despite treatment intensification, the patient experienced a hypocalcaemic crisis during hospitalisation. Teriparatide treatment at 2 × 20 µg/day resulted in the resolution of tetany symptoms, with gradual normalisation of calcium-phosphate balance parameters during the following days. CONCLUSIONS: Based on the analysis of these cases, the conclusion was drawn that the use of recombinant human teriparatide allows for the control of severe hypocalcaemia requiring intravenous infusions of calcium in patients with postoperative hypoparathyroidism. (Endokrynol Pol 2016; 67 (4): 403-412).

Cerebrospinal meningitis in a 30 -year -old patient as first manifestation of pituitary macroadenoma.

Introduction: The most common clinical and neurological signs and symptoms of pituitary macroadenomas include headache, vision impairment and cranial nerve palsy. Case report: The patient presented in this article was admitted to the Intensive Care Unit at regional hospital; at admission, the patient was unconscious, he had convulsions and spasms, and a 3 -day history of headache and body temperature up to 41.5°C. The patient with suspected neuroinfection was transferred to the Department of Infectious Diseases of the Pomeranian Medical University in Szczecin (PMU), where cerebrospinal meningitis of bacterial etiology was established based on cerebrospinal fluid investigations and the presence of pituitary abscess was suggested based on magnetic resonance imaging (MRI). Magnetic resonance imaging findings included an extensive pathological lesion with the diameter of 27 × 28 × 38 mm located in the sellar-suprasellar region, with intensive peripheral contrast enhancement. The lesion protrudes into the sphenoid sinus through the lowered bottom of sella turcica and the fluid content has also been visualized in the sphenoid sinus. After 10 -day antibiotic therapy, the patient was transferred to neurosurgery ward for surgical treatment. The pathological lesion was partially evacuated during right frontotemporal craniotomy. The patient's general condition after the surgery was moderately severe; the patient was conscious, able to follow simple commands, presenting hemiparesis of the left side of the body, particularly affecting left lower limb and with speech disturbances. The signs of hypopituitarism affecting all hormonal axes were also observed and the patient was transferred to the Department of Endocrinology of the PMU for further treatment. Follow -up MRI scan continued to show the presence of pathological mass in the sellar -suprasellar region, which penetrated into the sphenoid sinus through damaged sellar bottom. After correction of reduced hormone levels and several weeks of antibiotic therapy, the patient was transferred to the Department of Neurosurgery of the PMU for further surgical treatment. Transsphenoidal resection of the sellar -suprasellar tumor and sphenoid sinus reconstruction were performed. Histopathology report confirmed the diagnosis of pituitary adenoma. The patient in relatively good condition, with partial hemiparesis on the left side of the body, able to stand with support, not able to walk, with speech disturbances and able to follow commands was transferred to the rehabilitation center. One year later, follow- -up MRI scan showed deepened sella turcica, filled with a mass corresponding to postoperative material. No evidence of disease progression has been found. Conclusion: Neuroinfection may be the first manifestation of pituitary macroadenoma.

Evaluaton of therapy with cabergoline in men with macroprolactinoa.

INTRODUCTION: Pituitary gland adenomas producing prolactin are one of the commonest hormonally active tumours. Pharmacological treatment using of dopamine receptors agonists is the therapy of choice in a case of prolactinoma. Bromocriptine, which causes numerous side-effects is the most commonly used drug. Recently, good results of therapy have been achieved with cabergoline - a selective dopamine receptor agonist with prolonged time of action. The aim of the study was to evaluate therapy with cabergoline of men with macroprolactinoma based on clinical, hormonal and radiological examinations. MATERIAL AND METHODS: Ten men aged 18-65 (mean 41.9 ?15.01 years) with the presence of a pathological mass in the pituitary gland sized between 16.7 and 40.5 mm (mean 29.8 ± 9.38 mm) and an elevated prolactin (PRL) level of between 37.3 and 4700 ng/mL (mean 1608.2 ±1771.6 ng/mL) were included in the study. The PRL and other trophic hormones levels were evaluated after 1, 3, 6 and 12 months, and tumour size was evaluated by magnetic resonance imaging examination after 12 months of therapy with cabergoline. Results: Therapy with cabergoline led to remission of headaches, visual acuity correction, and a significant improvement in libido and erection in all patients. In 90% of patients, PRL normalisation was achieved, just the initial months of therapy. The mean PRL serum concentrations were before, and after 1, 3, 6 and 12 months of therapy respectively, 1608.2 ± 1771.6 ng/mL and 263.4 ± 223.4, 136.1 ± 244.7,91.31 ± 105.5 and 27.5 ± 57.7 ng/mL. A significant tumour size reduction was observed: from 29.8 ± 9.4 mm to 23.2 ± 9.4 mm, a mean reduction of about 6 mm, or 25.1% (from 4-48.5%). No significant correlation between the mean tumour size and PRL level was observed before or during the treatment. A decreased testosterone level before the therapy was proven, and its gradual increase during the treatment was observed, but after 12 months no normal mean testosterone concentration was achieved. CONCLUSIONS: 1. The administration of cabergoline to patients with macroprolactinoma is effective in reaching PRL level normalisation as well as in tumour size reduction. 2. Therapy with cabergoline significantly decreases the clinical symptoms of hyperprolactinemia and neurological and ophtalmological changes associated with the presence of a pathological lesion in the pituitary gland. 3. Tumour size is not a predictive factor for the effectiveness of therapy with cabergoline.

Late diagnosis of type 2B multiple endocrine neoplasia (MEN 2B) in a 23 year-old patient.

We present a case of MEN 2B diagnosed in a 23 year-old patient on the basis of bilateral pheochromocytoma and medullary thyroid carcinoma. This young male patient also had multiple paragangliomas located along the spine, marfanoid features of body habitus and numerous mucosal neuromas of the oral cavity and intestinal ganglioneuromatosis. The patient was hospitalised several times between the ages of 11 and 14 due to heart rhythm disorders (tachycardia, multiple supraventricular beats) and pain in the precardiac area. Elevated blood pressure was not observed at that time. In 2010, the patient was admitted to hospital due to abdominal pain, nausea, vomiting and hypertension; bilateral adrenal tumours were then detected. The patient was referred to the Department of Endocrinology in Szczecin, with suspected pheochromocytoma in order to continue the diagnostic process. This resulted in the diagnosis of bilateral pheochromocytoma and medullary thyroid carcinoma. On the basis of the whole clinical picture, the diagnosis of MEN 2B was established and subsequently confirmed with genetic test results. Following the removal of adrenal tumours and thyroidectomy, the patient was referred to the Cancer Centre and Institute of Oncology in Gliwice for further treatment (X-ray therapy and further surgery due to recurrence of medullary carcinoma). This article presents a case of late MEN 2B diagnosis despite the presence of clinical symptoms suggestive of Multiple Endocrine Neoplasia observed from early childhood.

From open to laparoscopic adrenalectomy: thirty years' experience of one medical centre.

INTRODUCTION: Laparoscopic adrenalectomy (LA) has become the standardized treatment of benign adrenal lesions over the last two decades, making the indications to open adrenalectomy (OA) limited. The purpose of this study was to show the thirty years of experience in open (OA) and laparoscopic adrenalectomy (LA) gained in one medical centre as well as to compare the results of OA and LA performed for benign adrenal lesions. MATERIAL AND METHODS: Three hundred patients underwent 127 open and 173 laparoscopic adrenalectomies between 1979 and 2009 at M. Curie Hospital in Szczecin, Poland. Analyzed factors included patients demographic data, ASA score, indication for surgery, tumour size and side, characteristics of the removed tumours, intraoperative and postoperative outcome of LA and OA, postoperative pain sensation, intraoperative and postoperative complications, and conversion rate from LA to OA. Tumours with diameter exceeding 8 cm were excluded. RESULTS: There were no significant differences regarding the analyzed preoperative data in both groups of patients. The mean operative time was longer in the LA group (137 v. 82 min., p < 0.0001) and the blood loss was lower in LA group (110 v. 254 mL, p < 0.0001). The mean time until resumption of normal diet was shorter after LA (22 v. 44 h), as was the mean time until ambulation (17 v. 36 h), mean length of the hospital stay (4.6 v. 6.8 days), and mean time until return to normal activities (14 v. 23 days, p < 0.0001 for each difference). The analgesic requirement on the first and the second day postoperatively was lower in the LA group (p < 0.0001). The incidence of intraoperative and postoperative complications did not differ significantly between both analyzed groups. The rate of the conversion from LA to OA was 16%. The histopathological diagnosis was adenoma of the adrenal gland in the majority of cases. CONCLUSIONS: This study shows that LA is a safe, effective, and well-tolerated procedure. It may be recommended as a "gold standard" surgery in a case of benign functioning or non-functioning adrenal tumours with diameter less than 8 cm. (Pol J Endocrinol 2010; 61 (1): 94-101).

Influence of modified transdermal hormone replacement therapy on the concentrations of hormones, growth factors, and bone mineral density in women with osteopenia.

The metabolic and therapeutic action of estrogens depends on their type, dosage, form, route of administration, and treatment-free interval during the therapeutic cycle. Hormone therapy is generally subclassified into 2 forms that differ in the type of hormones. In hormonal replacement therapy (HRT), estrogens and progesterone components do not differ in chemical structure and molecular mass from those naturally produced by the female organism. In hormonal supplementary therapy (HST), the estrogen and progestagen components do differ from the natural hormones in structure and mass. The aim of the study was to compare 2 kinds of hormonal therapy in early postmenopausal women with osteopenia. These forms of therapy are modified transdermal HRT and orally given HST. The objective of this study was the estimation of sex hormone, insulin-like growth factor I (IGF-I), prolactin (PRL), osteocalcin, and procollagen concentration in serum as well as the degree of mineralization of the lumbar spine in women in the early postmenopausal period with osteopenia under different kinds of hormonal therapy. The study was conducted in 75 women with an average age of 52.4 +/- 3.5 years and with primary osteopenia, in the early postmenopausal period, who were randomly assigned to 3 groups depending on the form and route of administration of therapy: Group I (n = 25, control) was receiving placebo in the form of patches. Group II (n = 25) was treated with modified transdermal HRT. This group obtained micronized 17beta-estradiol at increasing-decreasing doses and progesterone in the second phase of the therapeutic cycle. Group III (n = 25) was receiving orally given HST and obtained Cyclo-Menorette (Wyeth, Munster, Germany). The therapeutic cycle in each group lasted 21 days, followed by a 7-day medication-free interval. Estradiol concentration in serum was increased 5-fold and estrone (E(1)) was increased about 11-fold in the group of women receiving orally given HST (P < .0001) compared with control group. Estrone and estradiol levels were increased about 3-fold in women receiving modified transdermal HRT compared with the baseline values. Basal PRL concentration and PRL level after metoclopramide stimulation test significantly increased after 3 and 12 months of treatment in the group receiving orally given HST. In women receiving modified transdermal HRT, increased IGF-I concentrations were statistically significant after 3 months of treatment. In the group of women receiving orally given HST, a significant decrease of IGF-I after 1 year therapy was found. During the entire time of treatment in this group, an increase of growth hormone was observed. No significant changes were shown in osteocalcin and in carboxyterminal propeptide of type I procollagen in all groups. Increase in bone mineral density L(2)-L(4) was statistically significant in the group receiving modified transdermal HRT (P < .01) and was insignificant in women receiving orally given HST after 12 months of therapy as compared with baseline values. Following are the conclusions: (1) Low-dose modified transdermal HRT modulates concentration of hormones, growth factor, IGF-I, osteocalcin, procollagen, and bone metabolism. (2) The curve concentrations of estrogens and progesterone in serum are similar to the type observed in the physiologic menstrual cycle. (3) The lack of significant increase in bone mineral density of lumbar spine in women after HST may be a result of significantly lower concentration of IGF-I in serum and occurring hyperprolactinemia.

[Biochemical aspects of modified, transdermal replacement hormone therapy]. / Biochemiczne aspekty zmodyfikowanej, przezskórnej homonoterapii zastepczej.

OBJECTIVES: The aim of the study is to evaluate the influence of modified, transdermal, hormone replacement therapy [HRT] and hormone supplement therapy [HST] on concentration of FSH , LH, E1, E2, PR, IGF1, GH and bone density of lumbar vertebrae in women with osteopenia in postmenopausal period. MATERIAL AND METHODS: 65 women were enrolled, aged from 43 to 58, divided into three groups based on a randomized list. Group I control used transdermal placebo, group II used transdermal hormonal therapy [HRT] and group III used hormonal therapy per oss [HST]. The concentrations of hormones were estimate by radioimmunoenzymatic methods. Statistic analysis was based on Statistical PL. RESULT: After transdermal hormonal therapy [HRT], the concentration of hormones is normalized and there is a significant increase of bone density of lumbar vertebrae. Hormonal supplement therapy per oss [HST]. There is the decrease of IGF1, BMD, and increase of concentrations of estrogens, prolactin, GH. CONCLUSION: 1. Transdermal, hormone replacement therapy [HRT] modulates concentration of sex hormones and bone metabolism. 2. Hyperestrogenism, hyperprolactinemia, decreased IGF1 concentration and low mineral density in women after HST may cause disorders of chemical estrogens metabolism.

Does the type of hormone replacement therapy affect lipoprotein (a), homocysteine, and C-reactive protein levels in postmenopausal women?

BACKGROUND: The results of studies evaluating the effect of hormone replacement therapy (HRT) on the cardiovascular risk raise many controversies. This may be related to both the type of treatment used and the disregard of additional risk factors. OBJECTIVE: The objective of the study was to evaluate the effect of natural estrogens taken transdermally and synthetic estrogens taken orally on the concentrations of lipoprotein (a) [Lp(a)], homocysteine, and C-reactive protein (CRP) in healthy women in the early postmenopausal period. Material The study was conducted on 61 healthy women with average age of 52.3 +/- 4.1 years, in the postmenopausal period, who were randomly assigned to 3 groups depending on the type and route of administration of the products. Group I (n = 24) was administered transdermal estrogens (micronized 17beta-estradiol; Systen, Janssen-Cilag, Switzerland) and progesterone in the second phase of the cycle. Group II (n = 21) was administered oral hormones (Cyclo-Menorette). Group III (n = 16), serving as a control, included women taking placebo in the form of patches. In each group, therapeutic cycles took 22 days and were followed by a treatment-free interval of 7 to 10 days for a 3-month period. RESULTS: After 3 months of treatment, Lp(a) and homocysteine levels were not significantly different from the baseline, irrespective of the route of administration of estrogens or placebo. Both forms of HRT used indicate significant difference in changes of CRP concentration during 3 months of administration (analysis of variance P = .0356). CRP concentration values increased in the group of women using oral HRT from 1.22 to 2.68 mg/L. In the group of women using oral therapy, significantly more cases (61%) of increase in CRP concentration compared with 39% in the transdermal HRT group (chi(2) P = .015) were observed. CONCLUSIONS: On the basis of our observations, it appears that in women in the early postmenopausal stage with normal initial concentrations of Lp(a) and homocystein, the form of therapy used has no influence on values of these parameters. The 2 forms of HRT therapy differ in effect, which is expressed as a change in CRP concentration. A tendency to increase CRP values when using oral HRT is observed, while such an effect is not observed in case of transdermal therapy after 3 months.