A Textbook of Clinical Pharmacology and Therapeutics

ANTERIORPITUITARYHARMONES ANDRELATEDDRUGS 317

with symptoms caused by the release of pharmacologically
active substances from gastro-enteropancreatic tumours, includ-
ing patients with carcinoid syndrome, insulinoma, VIPoma or
glucagonoma. It reduces symptoms of flushing, diarrhoea or
skinrash, but does not reduce the size of the tumour. It is more
effective than bromocriptine(now mainly used in Parkinson’s
disease, see Chapter 21) in lowering somatotropin levels in
patients with acromegaly, but it is not generally an acceptable
alternative to surgery, and must be administered parenterally
(usually subcutaneously three times daily). It is also effective in
patients with TSH-secreting basophil tumours of the adeno-
hypophysis causing thyrotoxicosis (an extremely rare cause of
hyperthyroidism). It reduces portal pressure in portal hyper-
tension, and is effective in the acute therapy of bleeding
oesophageal varices. It is also used to reduce ileostomy diar-
rhoea and the diarrhoea associated with cryptosporidiosis in
AIDS patients. Gastro-intestinal side effects are minimized if
octreotideis given between meals. A long-acting microsphere
octreotideformulation in poly (alkyl cyanoacrylate) nanocap-
sules is administered intramuscularly once a month.

Adverse effects

These include:

• gastro-intestinal upset, including anorexia, nausea,
  vomiting, abdominal pain, diarrhoea and steatorrhoea;


• impaired glucose tolerance, by reducing insulin secretion;


• increased incidence of gallstones and/or biliary sludge
  after only a few months of treatment, especially at higher
  doses. Ultrasound evaluation of the gall bladder is
  recommended before starting therapy and if biliary
  symptoms occur during therapy.

GONADOTROPHINS

The human pituitary gland secretes follicle-stimulating hor-

mone (FSH) and luteinizing hormone (LH). FSH is a glyco-

protein which in females controls development of the primary

ovarian follicle, stimulates granulosa cell proliferation and

increases oestrogen production, while in males it increases

spermatogenesis. LH is also a glycoprotein. It induces ovula-

tion, stimulates thecal oestrogen production and initiates and

maintains the corpus luteum in females. In males, LH stimu-

lates androgen synthesis by Leydig cells, and thus has a role in

the maturation of spermatocytes and the development of sec-

ondary sex characteristics.

Human menopausal urinary gonadotrophin (HMG), human

chorionic gonadotrophin (HCG) and synthetic LH and recombi-

nant FSH (follitropin alfaandbeta) are all commercially avail-

able. They are used to induce ovulation in anovulatory women

with secondary ovarian failure in whom treatment with

clomifene(see Chapter 41) has failed. Treatment must be super-

vised by specialists experienced in the use of gonadotrophins

and be carefully monitored with repeated pelvic ultrasound

scans to avoid ovarian hyperstimulation and multiple pregnan-

cies. Gonadotrophins are also effective in the treatment of

oligospermia due to secondary testicular failure. They are, of

course, ineffective in primary gonadal failure.

GONADORELIN ANALOGUES

Gonadorelin (gonadotrophin-releasing hormone, GnRH) is the

FSH/LH-releasing factor produced in the hypothalamus. It may

be used in a single intravenous dose to assess anterior pituitary

reserve. Analogues of GnRH (Table 42.1) such as goserelin,

buserelinandleuprorelinare also used to treat endometrio-

sis, female infertility (see Chapter 41), prostate cancer and

advanced breast cancer (see Chapter 48). Buserelinis given

intranasally, andgoserelinis usually given by subcutaneous

injection/implant into the anterior abdominal. In benign condi-

tions use should be limited to a maximum of six months because

reduced oestrogen levels lead to reduced bone density, in addi-

tion to menopausal-type symptoms (see below). For indications

such as endometriosis, it is possible to combine a GnRH ana-

logue with low-dose oestrogenreplacement to avoid this.

Mechanism of action

GnRH analogues initially stimulate the release of FSH/LH,

but then downregulate this response (usually after two weeks)

Key points

Growth hormone (GH, somatropin)

• Somatropin (recombinant GH) is used to treat short
  stature due to:
  
  
  • GH deficiency;
  
  
  • Turner’s syndrome;
  
  
  • Prader–Willi syndrome;
  
  
  • chronic renal impairment;
  
  
  • children who were born small for gestational age.
  
  
  
  


• Somatropin is also used for adults with severe
  symptomatic GH deficiency.


• GH secretion is controlled physiologically by:
  
  
  • somatorelin (stimulates GH secretion);
  
  
  • somatostatin (inhibits GH secretion).
  
  
  
  


• Somatostatin is secreted by D cells in the islets of
  Langerhans, as well as centrally, and inhibits the
  secretion of many gut hormones in addition to GH.


• Octreotide is a somatostatin analogue used:
  
  
  • in acromegalics with persistent raised GH despite
    surgery/radiotherapy;
  
  
  • in functional neuroendocrine tumours (e.g.
    carcinoid, VIPomas, glucagonomas);
  
  
  • to reduce portal pressure in variceal bleeding
    (unlicensed indication).
  
  
  
  


• Pegvisomant is a specific GH receptor antagonist: it is used
  for acromegaly when conventional treatment has failed.

Table 42.1:GnRH analogues

Drug Use and additional comments

Goserelin Used to treat endometriosis, prostate

cancer and advanced breast cancer

Leuprorelin Used to treat endometriosis and

prostate cancer

Buserelin Used to treat endometriosis. Prostate

cancer. Induction of ovulation prior

to IVF