Nina Rosa Musolino

Prolactinomas and Pregnancy

Prolactinomas are the most frequent pituitary tumors. Treatment of infertility in such tumors usually is very successful. On the other hand, reports of pituitary tumor growth during pregnancy have been described since bromocriptine started to be used. Since then, dopamine agonists (DA) have been increasingly used as the first-choice treatment of prolactinomas, with surgery being reserved for resistance or persistent intolerance to DA or for special situations. More recently other DA, such as quinagolide and cabergoline have shown better tolerance than bromocriptine with similar or greater efficacy. Cabergoline is now the first choice drug but its use in pregnancy is still under evaluation. We followed 71 term pregnancies in women bearing microprolactinomas. Of the 22 patients with previous surgery, none presented symptoms of tumor growth. Of the 41 pregnant patients treated with bromocriptine alone, only one (2.4%) presented with headaches, which regressed with drug reintroduction. Fifty one term pregnancies in patients with macroprolactinomas were followed by us. Of those, 21 were in patients with previous surgery and none of them presented clinical evidence of tumor growth. On the other hand, of the 30 patients treated only with pre-gestational bromocriptine, 11 (37%) manifested complaints related to tumor growth. A non-hormonal contraceptive should be the use along with a DA drug until tumor shrinkage within sellar boundaries has been evidenced. After pregnancy has been confirmed, the DA can be withdrawn and the patient must be closely followed. If tumor expansion is suspected, confirmation can be made through MRI and by visual field testing. Reintroduction of bromocriptine in such cases can lead to tumor reduction and clinical improvement. Surgery can also be employed as treatment for symptomatic tumor growth in pregnancy.

Treatment of acromegaly with octreotide‐LAR: extensive experience in a Brazilian institution

Objective  Somatostatin analogues have become the mainstay of the medical treatment of acromegaly. The aim of our study was to evaluate the efficacy and tolerability of octreotide‐LAR (OCT‐LAR) treatment in acromegalic patients.

Medical Management of Pituitary Adenomas: The Special Case of Management of the Pregnant Woman

The development of efficacious surgical and medical therapies for pituitary adenomas as well as the improvement of hormone therapy for ovulation induction has made pregnancy possible for women harboring pituitary tumors. However, gestational risks due to the possibility of tumor growth during pregnancy, mainly in women with macroadenomas, raise a concern. Bromocriptine has a well-established role for prolactinoma treatment before and during pregnancy, even when a symptomatic tumor increase occurs. It can also be used in acromegaly, despite its poorer results. Somatostatin analogs have been used in acromegaly even during pregnancy with uneventful outcomes, but their safety in pregnancy is not well established, yet. The largest experience with medical treatment for Cushings disease during pregnancy involves metyrapone, a steroidogenesis inhibitor, without descriptions of congenital abnormalities. Concerning clinically non-functioning pituitary tumors, ovulation induction or even in vitro fertilization are frequently needed. The purpose of this review is to provide an update on therapeutic strategies to restore fertility as well as gestational and post-gestational management of patients with pituitary adenomas, focusing mainly on the role of medical treatment for different tumor types.

Impact of recombinant human growth hormone (rh-GH) treatment on psychiatric, neuropsychological and clinical profiles of GH deficient adults: a placebo - controlled trial

BACKGROUND Untreated GH-deficient adults have a diversity of dysfunctions (e.g. reduced muscle strength, emotional instability during stress, depressive symptoms) that may cause deleterious effects on quality of life, and may be positively influenced by recombinant human growth hormone (rh-GH) therapy. AIM To evaluate the impact of a clinical intervention with rh-GH therapy on GH- deficient adults. METHOD The physical, psychiatric and neuropsychological status of 9 GH-deficient adults was determined before and after the administration of rh-GH (0.250 IU/Kg/week) in a double blind placebo-controlled trial for six months. Patients then received rh-GH for a further period of 6 months and their status was re-evaluated. RESULTS Rh-GH was significant better than placebo at 6th month (p < 0.05), producing increased serum Insulin like growth factor-I (IGF-I) levels, reduced body mass index (BMI) and body fat, increased lean body mass and water, reduced waist/hip ratio and increased energy expenditure. The rh-GH therapy was also significantly better than placebo on depressive features as measured by the Hamilton Depression Scale (17-items) (p = 0.0431) and the Beck Depression Inventory (p = 0.0431). Neuropsychological evaluations showed significant improvements in measures of Attention: Digit Backward (p = 0.035), Verbal Fluency (FAS) (p = 0.02) and Cognitive Efficiency (WAIS-R tests): Vocabulary (p = 0.027), Picture Arrangements (p = 0.017), and Comprehension (p = 0.01) following rh-GH therapy. CONCLUSION The clinical, psychiatric, and neuropsychological impairments of untreated GH-deficient adults can be decreased by rh-GH therapy.

Does partial surgical tumour removal influence the response to octreotide-LAR in acromegalic patients previously resistant to the somatostatin analogue?

Objective  To compare the intrapatient response to the same dose of slow‐release octreotide (OCT‐LAR) before and after noncurative surgery in acromegalic patients who did not attain disease control after primary treatment with OCT‐LAR.

Pharmacokinetic profile of lanreotide Autogel® in patients with acromegaly after four deep subcutaneous injections of 60, 90 or 120 mg every 28 days

Objective  To investigate the pharmacokinetic profile of a prolonged release, aqueous Autogel® formulation of the somatostatin analogue lanreotide (Lan‐ATG).

Acromegaly: correlation between expression of somatostatin receptor subtypes and response to octreotide-lar treatment

About one-third of acromegalics are resistant to the clinically available somatostatin analogs (SA). The resistance is related to density reduction or different expression of somatostatin receptor subtypes (SSTR). This study analyzes SSTR’s expression in somatotrophinomas, comparing to SA response, hormonal levels, and tumor volume. We analyzed 39 somatotrophinomas; 49% were treated with SA. The most expressed SSTR was SSTR5, SSTR3, SSTR2, SSTR1, and SSTR4, respectively. SSTR1 and SSTR2 had higher expression in patients that had normalized GH and IGF-I. SSTR3 was more expressed in patients with tumor reduction. There was a positive correlation between the percentage of tumor reduction and SSTR1, SSTR2 and SSTR3 expression. Also, a positive correlation between SSTR2 mRNA expression and the immunohistochemical reactivity of SSTR2 was found. Our study confirmed the association between the SA response to GH and IGF-I and the SSTR2. Additionally, this finding was also demonstrated in relation to SSTR1.

Headache in acromegaly : dramatic improvement with the somatostatin analogue SMS 201-995

Two acromegalic patients with severe headache, persisting after pituitary adenomectomy followed by radiotherapy in one, were treated with the somatostatin analogue SMS 201-995. Both had been resistant to conventional headache therapy and experienced dramatic and rapid relief after the first injection of the analogue. This result persisted with long-term treatment of the drug. Although the mechanism of action of SMS 201-995 in pain remains unclear, the rapid and efficacious analgesic effect of this compound may be one more indication for its use in pituitary tumors associated with cephalalgias.

Role for postoperative cortisol response to desmopressin in predicting the risk for recurrent Cushing's disease

In the early postoperative period of Cushings disease patients, desmopressin may stimulate ACTH secretion in the remnant corticotrophic tumour, but not in nontumour suppressed cells.

Cerebrospinal fluid rhinorrhea occurring in long-term bromocriptine treatment for macroprolactinomas.

Two patients harboring invasive macroprolactinomas, on treatment with bromocriptine, developed cerebrospinal fluid rhinorrhea 16 and 17 months after the beginning of the medical therapy. Neither patient had previously been submitted to surgery or radiotherapy. The fistulae were surgically corrected. Cerebrospinal fluid leakage is a well-documented complication of pituitary tumors, mainly after surgery and/or radiotherapy, but the reports of its occurrence after primary treatment with bromocriptine are rare. Therefore, the possibility of this complication must be considered, especially in patients with invasive macroprolactinomas.