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Gynækomasti og Mandlig Hypogonadisme mandebryster-moed-nicklas-der-fik-bryster-som-11-aarig.

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2 Gynækomasti og Mandlig Hypogonadisme

3 http://livsstil.tv2.dk/sundhed/2016-05-03-hver-tredje-mand-har- mandebryster-moed-nicklas-der-fik-bryster-som-11-aarig

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5  Benign proliferation of glandular tissue, male breast.  Common in infancy, adolescence, middle-aged to elderly men.  Pseudogynecomastia: fat deposition, no glandular proliferation.  Must be differentiated from breast carcinoma Very often patients concern Klinefelter / adipositas / langvarig gynækomasti GYNECOMASTIA

6  Hvorfor gik patienten til læge? - Frygt for cancer / ømhed / utilfreds med sit udseende. TAKE HOME MESAGES

7  Hvorfor gik patienten til læge?  If we don't get useful answers, we're not asking the right questions (kost tilskud / FMK).  Do no harm - T substitution may harm fertilitet / prostata / psyke / samliv.  Hypogonadisme: reversibel / irreversibel tilstand ??  Gel: Fysiologisk behandling - Nebido: ofte doping  Øm nyligt udviklet gynækomasti, overvej Tamoxifen. TAKE HOME MESAGES

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11 STIMULATION & INHIBITION

12 & INHIBITION

13  Op. Ve. kryptokisme før pubertet.  Fåresyge efter pubertet, bilat testis hævelse + ømhed  Op. Hø. lyskebrok.  Tilfælde 2003 med gynækomasti, nu nyt tilfælde, venstre side.  Sonografisk Holstebro gynækomasti bilat., in. prim. sin.  Henvist Herning udredning, omvisiteret hertil pga. ventetid.  Lab: markant forhøjede gonadotropiner. CASE 1

14  Ikke biologisk far, har adopteret.  Normalt samliv, ingen erektil dysfunktion, hedeture/svedeture eller nedsat sexlyst. Ingen kendt osteoporose.  Pt.s behov er at få udelukket malignitet.  Intet ønske om kirurgisk vurdering, hverken kosmetisk eller smertemæssigt. CASE 1

15  Ingen adipositas, tværtimod, Højde 186 cm, vægt 78 kg.  Ve. gynækomasti, intet malignt suspekt.  Ingen hudtrækninger, ingen palpable lymfeknuder i aksillen.  Frit forskydelig, ca. 3 x 4 cm, diskoid gynækomasti bag papillen.  Aktuelt ingen ømhed, i perioder kan der være let ømhed.  Penis nat., normal behåring. Testes små, venstre helt atrofisk.  UL: ingen tumores. Volumina: Ve. 3,5 ml, Hø. 7,1 ml. CASE 1

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19 REFERENCE INTERVALS

20 CASE 1

21 T SUBSTITUTION  Indikation.  Kontraindikationer ???  Enkelttilskud ved Primær Hypogonadisme  Gel / Kapsler / Injektion  Dosis  Monitorering: virkning / safety

22 NEBIDO (TEST. UNDECANOATE INJ.)

23  Hvorfor gik patienten til læge?  Hypogonadisme: reversibel / irreversibel tilstand ??  Tæt association mellem taljemål og T – Overvej søvnapnø, vægttab, depression  Gel: Fysiologisk behandling - Nebido: ofte doping TAKE HOME MESAGES

24  59 year-old previously healthy managing director.  1-2 months of tenderness, left mamma.  then tenderness, right side.  regression of the left side symptoms.  2011: hip alloplasty (arthrosis), meniscus lesion (not operated).  2012: disc herniation (laminectomy).  NSAID, never opioids or tramadole (fmk-online.dk).  3 children, no previous testicular issues. CASE 2

25  misses his appointment due to rehabilitation of disc herniation.  phone consultation, right sided symptoms persist.  LH 3.2 IU/l (mid normal), TT 8.6 nmol/l, FT 0.14 nmol/l.  other tests normal. Testes examination normal.  Hypogonadotropic hypogonadism ?? Strategy: what endocrinologists do best:  new appointment, new tests. CASE 2

26  All tests normal, including anterior pituitary hormones.  TT: 8.6 → 15.2 nmol/l,FT: 0.14 → 0.23 nmol/l.  left and right sided gynecomastia regressed. new tests and appointments or terminate examinations ?? can we explain the course ??  why arthrosis (and perhaps disc herniation and meniscus lesion) ?? CASE 2

27  intensive bicycling prior to injuries.  hundreds of kilometers every week.  patient uses the term ”extreme sport” himself. transient hypothalamic hypogonadism ?? aggravated by injury, anesthesia x 2, and ensuing inactivity ?? Well characterized phenomenon in women: hypothalamic amenorhoea CASE 2

28 95 DAY POLAR EXPEDITION

29 WELL CHARACTERIZED IN WOMEN

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31 CASE 3  80 year-old man, left gynecomastia for 4-5 months.  worried about malignancy.  some pain, but not the issue.  influenza, then pneumonia 2 months prior to symptoms.  arterial hypertension, ARB + thiazide diuretic  otherwise healthy  no overt symptoms of hypogonadism

32 CASE 3  not obese, no weight change, no Cushing stigmata.  2 x 2 cm palpable gynecomastia, no malignancy suspected.  TT 21.7 nmol/l, FT 0.24 nmol/l, SHBG 106 nmol/l  E 2 170 nmol/l (upper end of normal range)  LH 16 IU/L ( ↑ ), other lab parameters  normal testes examination.

33 CASE 3  increased SHBG by age: implication ?? SHBG higher affinity for T than E 2, thus: ↑ SHBG means relative increase in ratio of free E 2 / T.  reversible conditions: thyrotoxicosis, alcoholism, tobacco (hepatic cirrhosis).  increased LH is an indication of: T recovering from previously lower levels ?? hypergonadotropic hypogonadism ?? Should we treat (FT 0.24 nmol/l) indication of partial androgen insensitivity ?? drug induced gynecomastia ?? drug as important as in diagnostic work-up of hyperprolactinemia, Cushings syndrome, pheo, and primary hyperaldosteronism

34 Estrogen-like / binds to ER Stimulate estrogen synthesis Supply aromatizable estrogen precursors Testicular Damage Block T synthesis Block androgen action Displace estrogen from SHBG Estrogen- containing embalming cream Gonadotropins Exogenous androgen Busulfan Ketoconazole Flutamide Spironolactone Delousing powder Growth Hormone Androgen precursors: androstenedione DHEA Nitrosurea Spironolactone Bicalutamide Ethanol Digitalis VincristineMetronidazoleFinasteride Clomiphene Ethanol EtomidateCyproterone Marijuana Zanoterone Cimetidine Ranitidine Spironolactone

35 SPIRONOLACTON

36 UNCERTAIN ASSOCIATIONS Cardiac and antihypertensive medications: 1. Verapamil, nifedipine, diltiazem 2.ACE Inhibitors (captopril, enalapril) 3.Alpha- blockers 4.Amiodarone 5.Methyldopa 6.Reserpine 7.Nitrates Psychoactive drugs: 1.Neuroleptics 2.Anxiolytic agents e.g. Diazepam 3.Phenytoin 4.Tricyclic antidepressants 5.Haloperidol 6.Atypical antipsychotic agents Drugs for infectious diseases: 1.Antiretroviral therapy 2.Isoniazid 3.Ethionamide 4.Griseofulvin 5.Minocycline Drugs of Abuse: 1.Amphetamines 2.Heroin, Methadone Others: 1.Theophylline 2.Omeprazole 3.Domperidone 4.Penicillamine 5.Heparin 6.Methotrexate

37 CASE 3  Clinical decision: patients worry was fear of malignancy. pain, but no discomfort, no cosmetic issues. influenza and pneumonia prior to first symptoms can we explain the course ??  No significant endocrine abnormalities: patient had no wish of surgery agreement with patient: let’s waist and see. appointment 6 months hormones normal – complete regression

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40 MOST COMMON CAUSES  Persistent pubertal gynecomastia:25 %  Drugs / abuse:0 -25 %  No detectable abnormality:25 %  Cirrhosis or malnutrition:8 %  Primary hypogonadism:8 %  Secondary hypogonadism:2 %  Testicular tumors:3 %  Hyperthyroidism:1 -2 %  Chronic renal insufficiency:1 %

41 RARE CAUSES  Testicular Leydig cell tumor normal / low normal T normal / borderline elevated E 2 low / suppressed LH  Feminizing adrenocortical tumors (often malignant)  Ectopic hCG (pulmonary, gastric, renal neoplasms)  True hermaphroditism  Androgen insensitivity syndromes  Aromatase excess syndrome  Drug withdrawal (GnRH analogue for prostate cancer)

42  19 year-old man.  painful left gynecomastia for 18 months.  no abuse of marijuana, alcohol, tobacco, or banned substances.  history of right testicular atresia (confirmed laparoscopicaly).  no other symptoms of hypogonadism. CASE 4

43  professional football, knee injury, but no tramadole.  months with no training then “re-exposed”.  referral: LH high normal, FSH increased. borderline low TT and FT: 11.8 and 0.19 nmol/l (RIA). CASE 4

44  repeat analysis: LH high normal, FSH increased, TT 17.2 nmol/l (tandem MS). other normal (E 2, PRL, αFP, HCG, TSH, T4, hgb, liver, kidney) REFERENCE INTERVALS

45  normal anthropometrics (BMI 22.5, waist 90 cm).  firm left gynecomastia 2 x 2 cm.  no malignancy suspected.  empty right scrotum, normal left testis 15 ml.  testicular sonography? NO: normal E 2, normal tumor markers, no palpable mass. YES: history of undescented testis / increased FSH. CASE 4 Nordkap, Carlsen, Fedder, Jorgensen. Ugeskr Laeger 2012

46 TESTIC. MICROLITHS

47 TDS TESTICULAR DYSGENESIS SYNDROME

48  unilateral gynecomastia.  one testis with microlithiasis, one undescended / atretic.  initially borderline hypogonadism (initiation of training ??).  followed by normal biochemistry, except elevated FSH.  implications of microlithiasis: Risk of CIS, male infertility.  semen analysis ??Inhibin B ??biopsy ?? ABAB CASE 4 - STATUS

49  263 subfertile men  N=53 (20%) testicular microlithiasis. 23 unilateral, 30 bilateral.  no CIS or TGCT in 23 men with unilateral microlithiasis.  6 men with bilateral microlithiasis had CIS (20%).  prevalence in subfertile patients without microlithiasis is 0.5%.  CIS will transform to cancer testis in 50% of cases BILATERAL TESTICULAR MICROLITHIASIS PREDICTS THE PRESENCE OF THE PRECURSOR OF TESTICULAR GERM CELL TUMORS IN SUBFERTILE MEN. Gouveia Brazao et al. J Urol. 2004.

50  The bad news: azoospermia on more occasions. intratubular neoplasia / CIS confirmed.  the good news: few motile spermatozoea in biopsy, cryopreserved. gynecomastia regressed 3 months after first visit. FERTILITY CLINIC

51  watchfull waiting or therapy ??  which therapy: knife, drugs, or radiation ??  radiation, 16 Gy / 8 fractions, local.  recently: little suspicion of retroperitoneal lymph nodes on CT.  reffered for MRI.  lifelong follow-up for development of hypogonadism.  5 year follow-up, oncology. STRATEGY - CIS the most common cancer in young men. one of the most responsive to treatment. the only other causes of death that supersede testicular cancer in young men are trauma and suicide.

52  Hvorfor gik patienten til læge?  If we don't get useful answers, we're not asking the right questions (kost tilskud / FMK).  Do no harm - T substitution may harm fertilitet / prostata / psyke / samliv.  Hypogonadisme: reversibel / irreversibel tilstand ??  Gel: Fysiologisk behandling - Nebido: ofte doping  Udtalt øm, nyligt udviklet gynækomasti: overvej Tamoxifen. TAKE HOME MESAGES

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55  Neurofibromas  Lymphangiomas  Hematomas  Lipomas  Dermoid cysts RARE CONDITIONS DIFFERENTIAL DIAGNOSES

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57 TV2 Sundhed Cancer / ømhed / ønske om at se anderledes ud Take home mesages: Hvorfor gik patienten til læge fysik lærer: pinligt at tænde TV uden vide billedrør funk Afd. M: pinligt at hente pt i venteværelset uden at vide hv gik til læge If we don't get useful answers, we're not asking the right questions or the patient is not answering our questions honestly (case p-piller Louise) Do no harm - T substitution may harm (fertilitet / prostata / psyke / samliv) Fysiologisk behandling = gel - Nebido ofte = doping Øm nu-udviklet gynækomasti, overvej Tamoxifen. Reversibel / irreversibel tilstand Free Ø / Free T balance fØ / fT tissue / serum Testo / SHBG index afspejler ikke biologi / fysiologi Testosteron intratestikulært 50-100 x større konc. end i serum. Receptorer - PAIS / CAIS SHBG

58 Øget aromatisering, Pubertet, "pubertet i voksen alder" - langvarig sygdom Cases - hypergonadotrop hypogonadisme Klinefelter - alle aldre - SHOX (vs Turner), DXA, SELVMORD FORSØG Retentio testis / TDS / Orchitis / torsio / fertilitet / hustru kigger ned i jorden Opstart / modaliteter / ansøgning Strålebeh / c. testis / kemo (cisplatin / cyklophosphamid) Cases -Akro -Højt SHBG (thyreotox, cirrhose, accidental Ø, hæmatologi, EBV) -Nyretransplantation Livsstil (fe)Male athlete tria - for meget motion, for lidt mad, nedsat libido/gynækomasti BMI - Søvnapnø Drugs - spironolacton, c.prostatae Hash, Alkohol, Kost tilskud, fødevarestyrelsen, Anaboliske steroider Hypogonadisme er andet end low T (spermatogenese)


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